Heterodiamondoids

ABSTRACT

This invention is related to heteroatom containing diamondoids (i.e., “heterodiamondoids”) which are compounds having a diamondoid nucleus in which one or more of the diamondoid nucleus carbons has been substitutionally replaced with a noncarbon atom. These heteroatom substituents impart desirable properties to the diamondoid. In addition, the heterodiamondoids are functionalized affording compounds carrying one or more functional groups covalently pendant therefrom. This invention is further related to polymerizable functionalized heterodiamondoids. In a preferred aspect of this invention the diamondoid nuclei are triamantane and higher diamondoid nuclei. In another preferred aspect, the heteroatoms are selected to give rise to diamondoid materials which can serve as n- and p-type materials in electronic devices can serve as optically active materials.

This application is a divisional of U.S. patent application Ser. No.11/335,916, filed Jan. 18, 2006, which claims priority to U.S. patentapplication Ser. No. 10/622,130, filed Jul. 16, 2003, which claimspriority to 60/397,367, filed Jul. 18, 2002, the contents of which areincorporated herein by reference in their entirety.

FIELD OF THE INVENTION

This invention relates to heteroatom-containing diamondoids (i.e.,“heterodiamondoids”) which are compounds having a diamondoid nucleus inwhich one or more of the diamondoid nucleus carbons has beensubstitutionally replaced with a noncarbon such as a group IIIB,noncarbon group IVB, group VB or VIB atom. (Groups are based on theprevious IUPAC Periodic Table groups as referenced in Hawley's CondensedChemical Dictionary, 14^(th) ed. John Wiley & Sons, Inc, 2001.) Theseheteroatom substituents impart desirable properties to the diamondoid.In addition, the heterodiamondoids can be functionalized affordingcompounds carrying one or more functionalization groups covalentlypendant therefrom. Functionalized heterodiamondoids having polymerizablefunctional groups are able to form polymers containingheterodiamondoids.

In a preferred aspect the diamondoid nuclei are triamantane and higherdiamondoid nuclei. In another preferred aspect, the heteroatoms areselected to give rise to diamondoid materials which can serve as n- andp-type materials in electronic devices.

BACKGROUND INFORMATION

Diamondoids are cage-shaped hydrocarbon molecules possessing rigidstructures which are tiny fragments of a diamond crystal lattice.Adamantane is the smallest member of the diamondoid series and consistsof a single cage structure of the diamond crystal lattice. Diamantanecontains two adamantane subunits face-fused to each other, triamantanethree, tetramantane four, and so on. While there is only one isomericform of adamantane, diamantane and triamantane, there are four differentisomeric tetramantanes (i.e., four different shapes containing fouradamantane subunits). Two of the isomeric tetramantanes areenantiomeric. The number of possible isomers increases rapidly with eachhigher member of the diamondoid series.

Adamantane, which is commercially available, has been functionalized.For instance, U.S. Pat. No. 3,832,332 describes a polyamide polymerformed from alkyladamantane diamine; U.S. Pat. No. 5,017,734 discussesthe formation of thermally stable resins from ethynyl adamantanederivatives; and, U.S. Pat. No. 6,235,851 reports the synthesis andpolymerization of a variety of adamantane derivatives.

The following references related to adamantane and derivatives formedfrom adamantane:

-   Capaldi, et al., Alkenyl Adamantanes, U.S. Pat. No. 3,457,318,    issued Jul. 22, 1969-   Thompson, Polyamide Polymer of Diamino Methyl Adamantane and    Dicarboxylic Acid, U.S. Pat. No. 3,832,332, issued Aug. 27, 1974-   Baum, et al., Ethynyl Adamantane Derivatives and Methods of    Polymerization Thereof, U.S. Pat. No. 5,017,734, issued May 21, 1991-   Ishii, et al., Polymerizable Adamantane Derivatives and Process for    Producing Same, U.S. Pat. No. 6,235,851, issued May 22, 2001-   McKervey, et al., Synthetic Approaches to Large Diamondoid    Hydrocarbons, Tetrahedron 36, 971-992 (1980)-   Lin, et al., Natural Occurrence of Tetramantane (C ₂₂ H ₂₈),    Pentamantane (C₂₆H₃₂) and Hexamantane (C₃₀H₃₆) in a Deep Petroleum    Reservoir, Fuel 74:10, 1512-1521 (1995)-   Chen, et al., Isolation of High Purity Diamondoid Fractions and    Components, U.S. Pat. No. 5,414,189, issued May 9, 1995-   Balaban et al., Systematic Classification and Nomenclature of    Diamond Hydrocarbons—I, Tetrahedron 34, 3599-3606 (1978)-   Gerzon et al., The Adamantyl Group in Medicinal Agents, 1.    Hypoglycemic N-Arylsulfonyl-N-adamantylureas, Journal of Medicinal    Chemistry 6 (6), 760-763 (November 1963)-   Marshall et al., Further Studies on N-Arylsulfonyl-N-alkylureas,    Journal of Medicinal Chemistry 6, 60-63 (January 1963)-   Marshall et al., N-Arylsulfonyl-N-alkylureas, Journal of Organic    Chemistry 23, 927-929 (June 1958)-   Reinhardt, Biadamantane and Some of its Derivatives, Journal of    Organic Chemistry 27, 3258-3261, (September 1962)-   Sasaki et al., Synthesis of Adamantane Derivatives. II. Preparation    of Some Derivatives from Adamantylacetic Acid, Bulletin of the    Chemical Society of Japan 41:1, 238-240 (June 1968)-   Stetter et al, Ein Beitrag zur Frage der Reaktivitat von    Bruckenkopf-Carboniumionen, Uber Verbindungen mit    Urotropin-Struktur, XXVI, Chem. Ber. 96 550-555, (1963)-   Hass et al, Adamantyloxycarbonyl, a New Blocking Group. Preparation    of 1-Adamantyl Chloroformate, Journal of the American Chemical    Society 88:9, 1988-1992 (May 5, 1966)-   Stetter et al, Neue Moglichkeiten der Direktsubstitution am    Adamantan, Uber Verbindungen mit Urotropin-Struktur, XLIII, Chem.    Ber. 102 (10), 3357-3363 (1969)-   von H. U. Daeniker, 206. 1-Hydrazinoadamantan, Helvetica Chimica    Acta 50, 2008-2010 (1967)-   Stetter et al, Uber Adamantan-phosphonsaure-(1)-dichlorid, Uber    Verbindungen mit Urotropin-Struktur, XLIV, Chem. Ber. 102 (10),    3364-3366 (1969)-   Lansbury et al, Some Reactions of ∀-Metalated Ethers, The Journal of    Organic Chemistry 27:6, 1933-1939 (Jun. 12, 1962)-   Stetter et al, Herstellung von Derivaten des 1-Phenyl-adamantans,    Uber Verbindungen mit Urotropin-Struktur, XXXI, Chem. Ber. 97 (12),    3488-3492 (1964)-   Nordlander et al, Solvolysis of 1-Adamantylcarbinyl and    3-Homoadamantyl Derivatives. Mechanism of the Neopentyl Cation    Rearrangement, Journal of the American Chemical Society 88:19 (Oct.    5, 1966)-   Sasaki et al, Substitution Reaction of 1-Bromoadamantane in Dimethyl    Sulfoxide: Simple Synthesis of 1-Azidoadamantane, Journal of the    American Chemical Society 92:24 (Dec. 2, 1970)-   Chakrabarti et al, Chemistry of Adamantane. Part II. Synthesis of    1-Adamantyloxyalkylamines, Tetrahedron Letters 60, 6249-6252 (1968)-   Stetter et al, Derivate des 1-Amino-adamantans, Uber Verbindungen    mit Urotropin-Struktur, XXIV, Chem. Ber. 95, 2302-2304 (1962)-   Stetter et al, Zur Kenntnis der Adamantan-carbonsaure, Uber    Verbindungen mit Urotropin-Struktur, XVII, Chem. Ber. 93, 1161-1166    (1960)-   Makarova et al, Psychotropic Activity of Some Aminoketones Belonging    to the Adamantane Group, Pharmaceutical Chemistry Journal, 34:6    (2000)

As noted above, heterodiamondoids are those diamondoids in which atleast one cage carbon atom is replaced by a heteroatom. The followingreferences describe more details about heteroadamantanes andheterodiamantanes.

-   Meeuwissen et al, Synthesis of 1-Phosphaadamantane, Tetrahedron    Letters, 39:24, 4225-4228 (1983)-   Boudjouk et al, The Reaction of Magnesium with    cis-1,3,5-Tris(bromomethyl)cyclohexane. Evidence For a Soluble    Tri-grignard, Journal of Organometallic Chemistry 281, C21-C23    (1985)-   Boudjouk et al, Synthesis and Reactivity of 1-Silaadamantyl Systems,    Journal of Organometallic Chemistry 2, 336-343 (1983).-   Krishnamurthy et al, Heteroadamantanes. 2. Synthesis of    3-Heterodiamantanes, Journal of Organometallic Chemistry, 46:7,    1389-1390 (1981)-   Udding et al, A Ring-opening Reaction of and Some Cyclisations to    the Adamantane System. A Quasi-favorsky Reaction of a ∃-bromoketone,    Tetrahedron Letters 55, 5719-5722 (1968)-   Blaney et al, Chemistry of Diamantane, Part II. Synthesis of    3,5-disubstituted Derivatives, Synthetic Communications 3:6, 435-439    (1973)-   Henkel et al, Neighboring Group Effects in the ∃-halo Amines.    Synthesis and Solvolytic Reactivity of the anti-4-Substituted    2-Azaadamantyl System, Journal of Organometallic Chemistry 46,    4953-4959 (1981)-   Becker et al, A Short Synthese of 1-azaadamantan-4-one and the 4r    and 4s Isomers of 4-Amino-1-azaadamantane, Synthesis, (11),    1080-1082 (1992)-   Eguchi et al, A Novel Route to the 2-Aza-adamantyl System via    Photochemical Ring Contraction of Epoxy 4-Azahomoadamantanes,    Journal of Organometallic Chemistry, Commun , 1147-1148 (1984)-   Gagneux et al, 1-Substituted 2-Heteroadamantanes, Tetrahedron    Letters 17, 1365-1368 (1969)-   Bubnov et al, A Novel Method of Synthesis of 1-azaadamantane from    1-boraadamantane, Journal of Organometallic Chemistry 412, 1-8    (1991).-   Sasaki et al, Synthesis of Adamantane Derivatives. 39. Synthesis and    Acidolysis of 2-Azidoadamantanes. A Facile Route to    4-Azahomoadamant-4-enes, Heterocycles 7:1 315-320 (1977)-   Sasaki et al, Synthesis of Adamantane Derivatives. 47. Photochemical    Synthesis of 4-Azahomoadamant-4-enes and Further Studies on Their    Reactivity in Some Cycloadditions, Journal of Organometallic    Chemistry, 44:21, 3711-3712 (1979)-   German Patent No. DE 2,545,292 issued April, 1979-   Suginome et al, Photoinduced Transformations. 73. Transformations of    Five- (and Six-) Membered Cyclic Alcohols into Five- (and Six-)    Membered Cyclic Ethers—A New Method of a Two-Step Transformation of    Hydroxy Steroids into Oxasteroids, Journal of Organometallic    Chemistry 49, 3753-3762, (1984)

Adamantane and substituted adamantane are the only readily availablediamondoids. Diamantane and triamantane and substituted diamantanes havebeen studied, and only a single tetramantane has been synthesized. Theremaining diamondoids were provided for the first time by the inventorsDahl and Carlson, and are described for example, in U.S. PatentApplication Ser. No. 60/262,842 filed Jan. 19, 2001 and PCT US02/00505filed 17 Jan. 2002.

SUMMARY OF THE INVENTION

The invention provides heterotriamantanes and hetero higher diamondoids.Heteroatoms are selected from atoms of group III B elements such as B orAl; noncarbon group IV B elements such as Si; group V B elements such asN, P or As, and particularly N or P; and group VI B elements such as O,S, or Se. It will be noted that the group VB elements are generallyclassed as electron-donating (hole-accepting) or “electropositive” atomsand the group III B elements are generally classed as electron-accepting(hole-donating) or “electronegative” atoms.

These heterodiamondoids of the invention are a triamantane or a higherdiamondoid nucleus with 1 or more (for example 1 to 20 and especially 1to 6) of its cage carbons replaced by a heteroatom. Theheterodiamondoids can also be substituted with up to 6 alkyl groups perdiamondoid unit.

This invention is further directed to functionalized heterodiamondoids.In this embodiment the heterotriamantanes and higher heterodiamondoidscontain at least 1 and, preferably 1 to 6 functional group(s) covalentlybonded to cage carbons, presented as Formula I:

wherein, G is a heterotriamantane or a higher heterodiamondoid nucleuswith one or more heteroatoms as described; and, R¹, R², R³, R⁴, R⁵ andR⁶ are each independently selected from a group consisting of hydrogenand covalently bonded functional groups, provided that there is at least1 functional group. More preferably, the functionalizedheterodiamondoids contain either 1 or 2 functional groups and from 1 to6 heteroatoms.

These heterodiamondoids and functionalized heterodiamondoids can existas discrete individual molecules. They can also exist as crystallineaggregates. These crystalline structures can be pure heterodiamondoidsor pure functionalized heterodiamondoids or can, intentionally orinadvertendly, be a mixture of more than one diamondoid with or withoutfunctionalization, with heterodiamondoid and/or functionalizedheterodiamondoid.

Some of these functionalized heterodiamondoids can be prepared fromheterodiamondoids in a single reaction step. These materials arereferred to herein as “primary functionalized heterodiamondoids” andinclude, for example, heterodiamondoids of Formula I wherein thefunctionalizing groups are halogens (such as -bromos, and -chloros),-thios, -oxides, -hydroxyls, and -nitros, as well as other derivativesformed in one reaction from a heterotriamantane or a higherheterodiamondoid.

Others of these functionalized heterodiamondoids are materials preparedfrom a primary functionalized heterodiamondoids by one or moresubsequent reaction steps. These materials are referred to herein as“secondary functionalized heterodiamondoids.” It will be appreciatedthat in some cases one primary functionalized heterodiamondoid may beconveniently formed by conversion of another “primary” material. Forexample, a poly-bromo material can be formed either by single stepbromination or by several repeated brominations. Similarly, a hydroxylheterodiamondoid can be formed directly from a heterodiamondoid in onestep or can be prepared by reaction of a bromo-heterodiamondoid, adiamondoid-oxide or the like. Notwithstanding this, to avoid confusion,the “primary” materials will not be included here in the representativesecondary materials. They will, however, be depicted in various figuresshowing reactions for forming primary and secondary materials to depictboth routes to them.

Representative “secondary functionalized heterodiamondoid” functionalgroups include haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl,heteroaryl, alkylthio, alkoxy; aminoalkyl, aminoalkoxy,heterocycloalkoxy, cycloalkyloxy, aryloxy, and heteroaryloxy.

Other functional groups that can be present in the secondaryfunctionalized heterodiamondoids are represented by the formula —C(O)Zwherein Z is hydrogen, alkyl, halo, haloalkyl, halothio, amino,monosubstituted amino, disubstituted amino, cycloalkyl, aryl,heteroaryl, heterocyclic; —CO₂Z wherein Z is as defined previously;—R²COZ and —R⁷CO₂Z wherein R⁷ is alkenyl aminoalkenyl, or haloalkenyland Z is as defined previously; —NH₂; —NHR′, —NR′R″, —N⁺R′R″R′″ whereinR′, R″, and R′″ are independently alkyl, amino, thio, thioalkyl,heteroalkyl, aryl, or heteroaryl; —R⁸NHCOR⁹ wherein R⁸ is —CH₂—, —OCH₂—,—NHCH₂—, —CH₂CH₂—, —OCH₂CH₂— and R⁹ is alkyl, aryl, heteroaryl, aralkyl,or heteroaralkly; and —R¹⁰CONHR¹¹— wherein R¹⁰ is selected from —CH₂—,—OCH₂—, —NHCH₂—, —CH₂CH₂—, and —OCH₂CH₂—, and R¹¹ is selected fromhydrogen, alkyl, aryl, heteroaryl, aralkyl, and heteroaralkyl.

In a further preferred embodiment, the functional group on thefunctionalized heterodiamondoid is —COOR¹⁶ wherein R¹⁶ is alkyl, aryl,or aralkyl; —COR¹², wherein R¹⁷ is alkyl, aryl, or heteroalkyl; —NHNH₂;—R¹⁸NHCOR¹⁹ wherein R¹⁸ is absent or selected from alkylene, arylene, oraralkylene, R¹⁹ is hydrogen, alkyl, —N₂, aryl, amino, or —NHR²⁰ whereinR²⁰ is hydrogen, —SO₂-aryl, —SO₂-alkyl, SO₂ aralkyl or —CONHR²¹ whereinR²¹ is hydrogen, alkyl, aralkyl, or —CSNHR²¹ wherein R²¹ is as definedabove; and —NR²²—(CH₂)_(n)—NR²³R²⁴, wherein R²², R²³, R²⁴ areindependently selected from hydrogen, alkyl, and aryl, and n is from 1to 20.

In an additional embodiment, the functional group on the functionalizedheterodiamondoid may be independently selected from —N═C═S; —N═C═O;—R—N═C═O; —R—N═C═S; —N═S═O; R—N═S═O wherein R is alkyl; —PH₂; —PDX₂wherein X is halo; —PO(OH)₂; halo; —OSO₃H; —SO₂H; —SOX wherein X ishalo; —SO₂R wherein R is alkyl; —SO₂OR wherein R is alkyl; —SONR²⁶R²⁷wherein R²⁶ and R²⁷ are independently hydrogen or alkyl; —N₃; —OC(O)Cl;or —OC(O)SCl.

In further an additional embodiment, one or more of the functionalgroups on the functionalized heterodiamondoids may be of the formula:

wherein n is 2 or 3; X is oxygen, sulfur, or carbonyl; Y is oxygen orsulfur; and R⁸ is selected from the group consisting of hydrogen, alkyl,heteroalkyl, aryl, and heteroaryl.

In a further aspect, the functionalizing group may form a covalent bondto two or more of these heterodiamondoids and thus serve as a linkinggroup or polymerizable group between the two or more heterodiamondoids.This provides functionalized heterodiamondoids of formula II:

G-L-(G)_(n) or G-L-(D)_(n) or G-(L-G)_(n) or G-(L-D)_(n) or (G-L)_(n) orthe like  II

wherein D is a diamondoid nucleus, G is a heterotriamantane or a higherheterodiamondoid nucleus and L is a linking group and n is 1 or moresuch as 2 to 1000 and especially 2 to 500.

In this embodiment, the linking group L may be, for example, aryls,alkenyls, alkynyls, esters, amides, —N═C—N—;

wherein R²⁸, R²⁹, R³⁰, R³¹, R³², R³³ are independently hydrogen oralkyl, and n and m are independently from 2 to 20;

wherein R²⁸, R²⁹, R³⁰, R³¹, R³², and R³³ are hydrogen or alkyl; R³⁴,R³⁵, R³⁶, and R³⁷ are independently absent or hydrogen or alkyl with theproviso that at least one of R³⁴, R³⁵, R³⁶, and R³⁷ is present; and nand m are independently from 2 to 20 or the like.

In another aspect, the present invention relates to functionalizedheterodiamondoids of formula III:

(R′)_(n)-G-G′-(R″)_(m)  III

wherein G and G′ are each independently a heterodiamondoid nucleus andR′ and R″ are substituents on the heterodiamondoid nucleus and areindependently hydrogen or a functionalizing group. n and m are 1 or moresuch as 1 to 10 and preferably 1 to 6. More preferably the materialcontains either 1 or 2 functional groups. Preferably R′ and R″ are halo;cyano; aryl; arylalkoxy; aminoalkyl; or —COOR⁴⁰ wherein R⁴⁰ is hydrogenor alkyl.

The heterodiamondoids and functionalized heterodiamondoids of thepresent invention are useful in for instance, nanotechnology, drugs,drug carriers, pharmaceutical compositions, precursors for the synthesisof biologically active compounds, photoresist materials and/orphotoresist compositions for far UV lithography, synthetic lubricants,heat resist materials and solvent-resistant resins, and so on. Forexample, these heterodiamondoid derivatives may have desirablelipophilic properties, which may improve the bioavailability ofpharmaceutically active groups attached thereto. These heterodiamondoidsand derivatives may also be useful as chemical intermediates for thesynthesis of further functionalized heterodiamondoids to form a varietyof useful materials. Such materials include composite matrix resins,structural adhesives and surface files that are used for aerospacestructural applications. Furthermore, coating layers or molded productswith excellent optical, electrical or electronic and mechanicalproperties are produced for use in optical fibers, photoresistcompositions, conduction materials, paint compositions and printinginks. In addition, these heterodiamondoid derivative-containingmaterials will have high thermal stability making them suitable for usein environments requiring such stability including for example, devicessuch as semiconductors, coatings for refractory troughs or other hightemperature applications.

In applications of particular importance, the heteroatoms introducedinto the triamantane of higher diamondoid nucleus are electron-donatingor electron-accepting. The semiconducting heterodiamondoids that resulthave utility in a variety of transistor and other electronic andmicroelectronic settings.

In addition, when the heteroatoms in the heterodiamondoids areelectron-donating, and particularly nitrogen, this gives rise to thepossibility that the donated electrons can be excited from the normalvalence bond through a bond gap into a conductive bond. When the excitedelectrons decay back to their base state, particularly if a vacancy isadjacent to the electron-donating heteroatom, a photon can be emitted.This suggests that these heterodiamondoids could have properties toprovide molecular size and crystallite-sized fluorescent species, lasingspecies and photodetecting species. (See Kurtsiefer, C, et al StableSolid-State Source of Single Photons, Physical Review Letters 85, 2,290-293 (2000).

BRIEF DESCRIPTION OF THE DRAWINGS

This invention will be further described with reference to the drawingsin which:

FIG. 1 shows the numbering of four tetramantanes and points outrepresentative secondary, tertiary and quaternary carbon atoms.

FIG. 2 presents exemplary computer modeling calculations that illustratethe feasibility of the synthesis of heterodiamondoids.

FIGS. 3-5 illustrate reaction routes for introducing an oxygenheteroatom into a diamondoid.

FIG. 6 illustrates routes for introducing a sulfur heteroatom into adiamondoid.

FIGS. 7-8 illustrate routes for introducing a nitrogen heteroatom into adiamondoid.

FIGS. 9-23 illustrate representative routes for functionalizingheterodiamondoids.

FIGS. 24-33 illustrate representative polymers containingheterodiamondoids and routes to prepare them.

FIG. 34 shows the total ion chromatogram (TIC) of the photohydroxylatedmixture of Example 2 containing hydroxylated tetramantanes includinghydroxylated alkyl tetramantanes.

FIG. 35 is the m/z 308 ion chromatogram showing the presence ofmonohydroxylated tetramantanes in the TIC of the reaction mixture ofExample 2.

FIG. 36 is the mass spectrum of a monohydroxylated tetramantane withGC/MS retention time of 19.438 minutes from FIG. 35. The base peak inthis spectrum is the m/z 308 molecular ion.

FIG. 37 is the m/z 322 ion chromatogram showing the presence ofmonohydroxylated methyltetramantanes in the TIC of the reaction productof Example 2.

FIG. 38 is the mass spectrum of monohydroxylated methyltetramantane fromFIG. 37 with GC/MS retention times of 19.998 minutes.

FIG. 39 shows the total ion chromatogram (TIC) of the oxatetramantane-containing reaction mixture also produced in Example 2.

FIG. 40 is the m/z 294 ion chromatogram showing the presence of oxatetramantanes in the TIC of the reaction product of Example 2.

FIG. 41 is the mass spectrum of an oxa tetramantane with GC/MS retentiontime of 17.183 minutes from FIG. 40.

FIG. 42 shows the total ion chromatogram (TIC) of the azahomotetramantane-ene-containing reaction mixture of Example 3.

FIG. 43 is the m/z 305 ion chromatogram showing the presence of azahomotetramantane-enes in the TIC of the reaction mixture of Example 3.

FIG. 44 is the mass spectrum of an azahomo tetramantane-ene with GC/MSretention time of 18.062 minutes from FIG. 43.

FIG. 45 is the m/z 319 ion chromatogram showing the presence of azahomomethyltetramantane-enes in the TIC of the reaction product.

FIG. 46 is the mass spectrum of an azahomo methyltetramantane-ene withGC/MS retention time of 18.914 minutes from FIG. 45.

FIG. 47 shows the total ion chromatogram (TIC) of the epoxy azahomotetramantane-containing reaction mixture produced in Example 3.

FIG. 48 is the m/z 321 ion chromatogram showing the presence of epoxyazahomo tetramantanes in the TIC of the reaction product of Example 3.

FIG. 49 is the mass spectra of an epoxy azahomo tetramantane with GC/MSretention times of 21.929 from FIG. 48.

FIG. 50 is the m/z 335 ion chromatogram showing the presence of epoxyazahomo methyltetramantanes in the TIC of a reaction product of Example3.

FIG. 51 is the mass spectrum of an epoxy azahomo methyltetramantane withGC/MS retention time of 21.865 minutes from FIG. 50.

FIG. 52 shows the total ion chromatogram (TIC) of the N-formyl azatetramantane-containing reaction mixture of Example 3.

FIG. 53 is the m/z 321 ion chromatogram showing the presence of N-formylaza tetramantanes in the TIC of the reaction product of Example 3.

FIG. 54 is the mass spectrum of a N-formyl aza tetramantanes with GC/MSretention time of 21.826 minutes from FIG. 53.

FIG. 55 is the m/z 335 ion chromatogram showing the presence of theN-formyl aza methyltetramantanes in the TIC of a reaction product ofExample 3.

FIG. 56 is the mass spectrum of a N-formyl aza methyltetramantane withGC/MS retention time of 21.746 minutes from FIG. 55.

FIG. 57 shows the total ion chromatogram (TIC) of the azatetramantane-containing reaction mixture produced in Example 3.

FIG. 58 is the m/z 293 ion chromatogram showing the presence of the azatetramantanes in the TIC of the reaction product shown in Example 3.

FIG. 59 is the mass spectrum of an aza tetramantane with GC/MS retentiontime of 19.044 minutes.

FIG. 60 is the m/z 307 ion chromatogram showing the presence of the azamethyltetramantanes in the TIC of a reaction product of Example 3.

FIG. 61 is the mass spectrum of an aza methyltetramantane with GC/MSretention time of 22.936 minutes.

FIG. 62 is the m/z 321 ion chromatogram showing the presence of the azadimethyltetramantanes in the TIC of a reaction product of Example 3.

FIG. 63 is the mass spectrum of an aza dimethyltetramantane with GC/MSretention time of 22.742 minutes from FIG. 62.

DETAILED DESCRIPTION OF THE INVENTION

This detailed description is presented in the following subsections:

Definitions

Synthesis of Heterodiamondoids

Functionalization of Heterodiamondoids and Derivatives Therefrom

Heterodiamondoid-Containing Polymers

DEFINITIONS

As used herein, the following terms have the following meanings.

The term “diamondoid” is given a special meaning. It refers tosubstituted and unsubstituted caged compounds of the adamantane seriesbeginning with triamantane and including, in addition, tetramantane,pentamantane, hexamantane, heptamantane, octamantane, nonamantane,decamantane, undecamantane and dodecamantane. A higher diamondoid istetramantane or higher. Substituted diamondoids preferably comprise from1 to 10 and more preferably 1 to 4 substituents independently selectedfrom the group consisting of alkyl, including linear (i.e., straightchain) alkyl, branched alkyl or cycloalkyl groups.

The term “heteroatom” refers to an atom selected from IIIB, non-C IVB,VB and VIB elements in the Periodic Table of the Elements, e.g. B, Al,Si, N, P, As, O, S, etc.

The terms “heterodiamondoid” and “hetero diamondoid” refer to diamondoid(as specifically defined) in which at least one cage carbon atom isreplaced by a heteroatom. Heterodiamondoids include heterotriamantane,heterotetramantane, heteropentamantane, heterohexamantane,heteroheptamantane, heterooctamantane, heterononamantane,heterodecamantane, heteroundecamantane, heteroundecamantane andheterododecamantane. Substituted heterodiamondoids preferably comprisefrom 1 to 10 and more preferably 1 to 4 substituents independentlyselected from the group consisting of alkyl, including linear (i.e.,straight chain) alkyl, branched alkyl or cycloalkyl groups.

The terms “functionalized heterodiamondoid” and “derivatizedheterodiamandoid” refer to a heterodiamondoid which has at least onecovalently bonded functional group.

The term “alkyl” refers to a linear saturated monovalent hydrocarbongroup having 1 to 40 carbon atoms, preferably 1 to 10 carbon atoms, morepreferably 1 to 6 carbon atoms; or a branched saturated monovalenthydrocarbon group having 3 to 40 carbon atoms, preferably from 3 to 10carbon atoms, and more preferably 3 to 6 carbon atoms. This term isexemplified by groups such as methyl, ethyl, n-propyl, iso-propyl,n-butyl, iso-butyl, n-hexyl, n-decyl, tetradecyl, and the like.

The term “functional group” refers to halos, hydroxyls, oxides, nitros,aminos, thios, sulfonyl halides, sulfonates, phosphines and the like, aswell as such groups attached to hydrocarbyl materials such as alkyls,alkenyls, alkyaryls and aryls with or without substitution.

Synthesis of Heterodiamondoids

Prior to attempting an actual synthesis, it is often advantageous toutilize the methods of molecular modeling and computational chemistry inorder to predict the properties of a desired molecule, and to facilitatethe design of a synthetic pathway. These methods calculate the potentialenergy surface of a molecule, which takes into account the forces ofinteraction between the constituent atoms.

After optimizing the molecular structure and calculating the minimizedenergy, the heat of formation was calculated. The results of anexemplary calculation for the hetero-iso-tetramantane are provided inthe table shown in FIG. 2. In FIG. 2, “X” represents a heteroatom thathas been inserted into the diamond lattice substitutionally. The secondcolumn of the table denotes the position where the heteroatom replaces ahost carbon atom, and these positions are either denoted “C-2” forsecondary positions, or “C-3” for tertiary positions. Identification ofsecondary and tertiary positions is shown with four representativediamondoids in FIG. 1 and FIG. 2. The third column of the table are theheats of formation in kcal/mol.

The present calculations serve to demonstrate that the preparation ofsuch compounds is synthetically feasible.

A similar set of calculations was made for thehetero-[121212121]decamantane, with the results shown in Table 1:

TABLE 1 Heteroatom Heat of formation (X) Position (Kcal/mol) C −76.08 OC-2 −103.45 S C-2 −58.71 Se C-2 −53.26 B C-2 −42.40 C-3 −31.76 N C-2−56.91 C-3 −48.15 P C-2 −28.44 C-3 −27.10 As C-2 −43.59 C-3 −44.52

Similar to the example above, those calculations indicate that thesynthesis of the heterodiamondoids are feasible.

A final example of a calculation is presented forhetero-[1212121212]undecamantane. For this particular isomer, theresults of the calculations are shown in Table 2. In this example, thesubstitution is made at either the secondary C-2 atom at position 25, orthe C-3 atom at position 26. The results of the calculation are shown inTable 2:

TABLE 2 Heteroatom Heat of formation (X) Position (Kcal/mol) C −79.81 OC-2 106.92 S C-2 61.95 Se C-2 56.82 B C-2 −45.45 C-3 −35.85 N C-2 −60.32C-3 −52.45 P C-2 −32.05 C-3 −29.80 As C-2 −47.70 C-3 −47.96

Once again, the calculations indicate that the synthesis is feasible.

Thus, molecular modeling calculations have demonstrated that it isfeasible to substitutionally position a boron, nitrogen, phosphorus,arsenic, oxygen, or sulfur heteroatom into the diamond lattice of adiamondoid.

Starting from the diamondoids, there are several methodologies for thesynthesis of heterodiamondoids such as oxa and thia diamondoids. Forexample, FIGS. 3-5 illustrate three different synthesis pathways tooxadiamondoids. FIG. 6 shows two different pathways to thiadiamondoids.For another example, FIGS. 7 and 8 show different ways to prepareazadiamondoids. It is understood that while in the FIGS. 3-8 onlyiso-tetramantane is shown as the starting diamondoid, triamantane andother higher diamondoids may also be used.

Nitrogen heterodiamondoids may be synthesized by the method of T. Sasakiet al., Synthesis of adamantane derivatives. 39. Synthesis andacidolysis of 2-azidoadamantanes. A facile route to4-azahomoadamant-4-enes, Heterocycles Vol. 7, No. 1, p. 315 (1977). Theprocedure consists of a substitution of a hydroxyl group with an azidefunction via the formation of a carbocation, followed by acidolysis ofthe azide product.

Another synthetic pathway is provided by T. Sasaki et al., Synthesis ofAdamantane Derivatives. XII. The Schmidt Reaction of Adamantane-2-one,J. Org. Chem. Vol. 35, No. 12, p. 4109 (1970).

Alternatively, a 1-hydroxy-2-azaadamantane may be synthesized from1,3-dibromoadamantane, as reported by A. Gagneux et al. in 1-Substituted2-heteroadamantanes, Tetrahedron Letters No. 17, pp. 1365-1368 (1969).This is a multiple-step process, wherein first the di-bromo startingmaterial is heated to a methyl ketone, which subsequently undergoesozonization to a diketone. The diketone is heated with four equivalentsof hydroxylamine to produce a 1:1 mixture of cis and trans-dioximes;this mixture is hydrogenated to the compound 1-amino-2-azaadamantanedihydrochloride. Finally, nitrous acid transforms the dihydrochloride tothe hetero-adamantane 1-hydroxy-2-azadamantane.

Alternatively, a 2-azaadamantane compound may be synthesized from abicyclo[3.3.1]nonane-3,7-dione, as reported by J. G. Henkel and W. C.Faith, in Neighboring group effects in the β-halo amines. Synthesis andsolvolytic reactivity of the anti-4-substituted 2-azaadamantyl system,in J. Org. Chem. Vol. 46, No. 24, pp. 4953-4959 (1981). The dione may beconverted by reductive amination (although the use of ammonium acetateand sodium cyanoborohydride produced better yields) to an intermediate,which may be converted to another intermediate using thionyl choloride.Dehalogenation of this second intermediate to 2-azaadamantane wasaccomplished in good yield using LiAlH₄ in DME.

A synthetic pathway that is related in principal to one useful in thepresent invention was reported by S. Eguchi et al. in A novel route tothe 2-aza-adamantyl system via photochemical ring contraction of epoxy4-azahomoadamantanes, J. Chem. Soc. Chem. Commun., p. 1147 (1984). Inthis approach, a 2-hydroxyadamantane is reacted with a NaN₃ basedreagent system to form the azahomoadamantane, with is then oxidized bym-chloroperbenzoid acid (m-CPBA) to give an epoxy 4-azahomoadamantane.The epoxy is then irradiated in a photochemical ring contractionreaction to yield the N-acyl-2-aza-adamantane.

An exemplary reaction pathway for synthesizing a nitrogen-containinghetero iso-tetramantane is illustrated in FIG. 7. It will be known tothose of ordinary skill in the art that the reaction conditions of thepathway depicted in FIG. 7 will be substantially different from those ofEguchi due to the differences in size, solubility, and reactivities oftetramantane in relation to adamantane. A second pathway available forsynthesizing nitrogen-containing heterodiamondoids is illustrated inFIG. 8.

A phosphorus-containing heterodiamondoid may be synthesized by adaptingthe pathway outlined by J. J. Meeuwissen et. al in Synthesis of1-phosphaadamantane, Tetrahedron Vol. 39, No. 24, pp. 4225-4228 (1983).It is contemplated that such a pathway may be able to synthesisheterodiamondoids that contain both nitrogen and phosphorus atomssubstitutionally positioned in the diamondoid structure, with theadvantages of having two different types of electron-donatingheteroatoms in the same structure.

After preparing the heterodiamondoids, they may be functionalized withat least one functional group. Representative pathways are provided inthe Examples. Additional disclosure of derivatization methods isprovided below and in FIGS. 9-23.

Functionalization of Heterodiamondoids and the Derivatives Therefrom

Table 3 provides a representative list of heterodiamondoid derivatives.

TABLE 3 Representative Heterodiamondoid Derivatives HETERODIAMONDOIDFUNCTIONAL GROUP hetero trimantane-hetero undecamantane —F heterotrimantane-hetero undecamantane —Cl hetero trimantane-heteroundecamantane —Br hetero trimantane-hetero undecamantane —I heterotrimantane-hetero undecamantane —OH hetero trimantane-heteroundecamantane —CO₂H hetero trimantane-hetero undecamantane —CO₂CH₂CH₃hetero trimantane-hetero undecamantane —COCl hetero trimantane-heteroundecamantane —SH hetero trimantane-hetero undecamantane —CHO heterotrimantane-hetero undecamantane —CH₂OH hetero trimantane-heteroundecamantane —NH₂ hetero trimantane-hetero undecamantane —NO₂ heterotrimantane-hetero undecamantane ═O (keto) hetero trimantane-heteroundecamantane —CH═CH₂ hetero trimantane-hetero undecamantane —C≡CHhetero trimantane-hetero undecamantane —C₆H₅ hetero trimantane-heteroundecamantane —NHCOCH₃ hetero trimantane-hetero undecamantane —NHCHOhetero trimantane-hetero undecamantane —CH₂Br hetero trimantane-heteroundecamantane —CH═CHBr hetero trimantane-hetero undecamantane —C≡CBrhetero trimantane-hetero undecamantane —C₆H₄Br hetero trimantane-heteroundecamantane —CH₂Cl hetero trimantane-hetero undecamantane —CH═CHClhetero trimantane-hetero undecamantane —C≡CCl hetero trimantane-heteroundecamantane —C₆H₄Cl hetero trimantane-hetero undecamantane —CH₂OHhetero trimantane-hetero undecamantane —C₆H₄OH hetero trimantane-heteroundecamantane —OCOCl hetero trimantane-hetero undecamantane —OCSClhetero trimantane-hetero undecamantane —OCH₃ hetero trimantane-heteroundecamantane —OCH₂CH₂NH₂ hetero trimantane-hetero undecamantane—OCH₂C(CH₃)₂N(CH₃)₂ hetero trimantane-hetero undecamantane —O(CH₂)₅NH₂hetero trimantane-hetero undecamantane —O(CH₂)₅NH₂HCl heterotrimantane-hetero undecamantane

hetero trimantane-hetero undecamantane

hetero trimantane-hetero undecamantane —OCH₂CH₂NHC(O)CH₃ heterotrimantane-hetero undecamantane —C≡N hetero trimantane-heteroundecamantane —CH₂CO₂H hetero trimantane-hetero undecamantane —CH₂CO₂CH₃hetero trimantane-hetero undecamantane —CF₃CO₂H hetero trimantane-heteroundecamantane —COCH₃ hetero trimantane-hetero undecamantane —N═C═Shetero trimantane-hetero undecamantane —N═C═O hetero trimantane-heteroundecamantane —N═S═O hetero trimantane-hetero undecamantane —PH₂ heterotrimantane-hetero undecamantane —POCl₂ hetero trimantane-heteroundecamantane —PO(OH)₂ hetero trimantane-hetero undecamantane —SO₂Hhetero trimantane-hetero undecamantane —OSO₃H hetero trimantane-heteroundecamantane —SO₂CH₃ hetero trimantane-hetero undecamantane —SOClhetero trimantane-hetero undecamantane —SO₂OCH₃ hetero trimantane-heteroundecamantane —SON(CH₃)₂ hetero trimantane-hetero undecamantane —N₃hetero trimantane-hetero undecamantane

hetero trimantane-hetero undecamantane

hetero trimantane-hetero undecamantane

hetero trimantane-hetero undecamantane

Heterodiamondoid-Containing Polymers

Polymerization of polymerizable heterodiamondoid derivatives to formheterodiamondoid-containing polymers is similar to what we have alreadydisclosed in U.S. patent application Ser. No. 10/046,486 filed on Jan.16, 2002 entitled “polymerizable higher diamondoid derivatives”, whichis hereby incorporated herein by reference. FIGS. 24-33 present someexemplary heterodiamondoid-containing polymers and the polymerizationreactions which provide them.

EXAMPLES

Example 1 describes a most universal route for isolating higherdiamondoids components which can be applied to all feedstocks usedherein. This process uses HPLC as its final isolation step.

Example 2 describes methods that could be used to prepare aoxadiamondoid from a diamondoid-containing feedstock.

Example 3 describes methods that could be used to prepare aazadiamondoid from a diamondoid-containing feedstock.

Examples 4-10 describe methods that could be used to prepareheterodiamondoids (e.g. oxa-, thia-, aza-diamondoids, etc.) fromdiamondoids.

Examples 11-46 describe methods that could be used to prepareheterodiamondoid derivatives.

Examples 47-64 describe methods that could be used to prepareheterodiamondoid-containing polymers.

Example 1

This Example has seven steps.

Step 1. Feedstock selection

Step 2. GCMC assay development

Step 3. Feedstock atmospheric distillation

Step 4. Vacuum fractionation of atmospheric distillation residue

Step 5. Pyrolysis of isolated fractions

Step 6. Removal of aromatic and polar nondiamondoid components

Step 7. Multi-column HPLC isolation of higher diamondoids

a) First column of first selectivity to provide fractions enriched inspecific higher diamondoids.

b) Second column of different selectivity to provide isolated higherdiamondoids.

This example is written in terms of isolating several hexamantanes butthe other higher diamondoids can be isolated using it, as well.

Step 1—Feedstock Selection

Suitable starting materials were obtained. These materials included agas condensate, Feedstock A, and a gas condensate containing petroleumcomponents, Feedstock B. Although other condensates, petroleums, orrefinery cuts and products could have been used, these two materialswere chosen due to their high diamondoid concentration, approximately0.3 weight percent higher diamondoids, as determined by GC and GC/MS.Both feedstocks were light colored and had API gravities between 19 and20° API.

Step 2—GC/MS Assay Development

Feedstock A was analyzed using gas chromatography/mass spectrometry toconfirm the presence of target higher diamondoids and to provide gaschromatographic retention times for these target materials. Thisinformation is used to track individual higher diamondoids throughsubsequent isolation procedures.

Step 3—Feedstock Atmospheric Distillation

A sample of Feedstock B was distilled into a number of fractions basedon boiling points to separate the lower boiling point components(nondiamondoids and lower diamondoids) and for further concentration andenrichment of particular higher diamondoids in various fractions.

Step 4—Fractionation of Atmospheric Distillation Residue by VacuumDistillation

The Feedstock B atmospheric residium from Step 3 (comprising 2-4 weightpercent of the original feedstock) was distilled into fractionscontaining higher diamondoids.

Step 5—Pyrolysis of Isolated Fractions

A high-temperature reactor was used to pyrolyze and degrade a portion ofthe nondiamondoid components in various distillation fractions obtainedin Step 4 thereby enriching the diamondoids in the residue. Thepyrolysis process was conducted at 450° C. for 19.5 hours.

Step 6—Removal of Aromatic and Polar Nondiamondoid Components

The pyrolysate produced in Step 5 was passed through a silica-gelgravity chromatography column (using cyclohexane elution solvent) toremove polar compounds and asphaltenes.

Step 7—Multi-Column HPLC Isolation of Higher Diamondoids

An excellent method for isolating high-purity higher diamondoids usestwo or more HPLC columns of different selectivities in succession.

The first HPLC system consisted of two Whatman M20 10/50 ODS columnsoperated in series using acetone as mobile phase at 5.00 mL/min. Aseries of HPLC fractions were taken.

Further purification of this HPLC fraction was achieved using aHypercarb stationary phase HPLC column having a different selectivity inthe separation of various hexamantanes than the ODS column discussedabove.

Example 2 Oxatetramantanes from a Feedstock Containing Tetramantanes(FIG. 3)

A fraction as described in Example 1 containing all of the tetramantanesincluding some alkyltetramantanes and hydrocarbon impurities wasobtained.

A solution of 200 mg of the above feedstock containing tetramantanes in6.1 g of methylene chloride was mixed with 4.22 g of a solution of 1.03g (13.5 mmol) of peracetic acid in ethyl acetate. While being stirredvigorously, the solution was irradiated with a 100-watt high intensityUV light. Gas evolution was evident from the start. The temperature wasmaintained at 40-45° C. for an about 21-hour irradiation period. Thenthe solution was concentrated to near dryness, treated twice insuccession with 10-mL portions of toluene and reevaporated to drynessfollowed by CH₂Cl₂ extraction (15 mL×2). The combined organic extractwas then dried over Na₂SO₄, Solvent was evaporated to almost dryness toyield a product which was subjected to GC/MS characterization showingthe presence of a mixture hydroxylated tetramantanes as shown in FIG. 3.The chromatograms and mass spectra illustrating the presence ofhydroxylated tetramantanes are provided as FIGS. 35-38.

To a portion of the hydroxylated tetramantanes in dry benzene (10 mL)was added mercury(II) oxide (100 mg) and iodine (170 mg). After theaddition, the reaction mixture was irradiated for about 7 h in anatmosphere of nitrogen by the procedure reported by Suginome et al. (J.Org. Chem., 1984, 49, 3753). Work-up gave a product mixture which wassubjected to GC/MS characterization showing the presence of theoxatetramantane product 3 of FIG. 3. The chromatogens and mass spectraare provided as FIGS. 39-41.

Example 3 Azatetramantanes from a Feedstock Containing a Mixture ofTetramantane Isomers

In the next step, an azahomo tetramantane-ene may be produced from theabove hydroxylated tetramantanes, or from photooxidized tetramantanes.To a stirred and ice cooled mixture of 98% methanesulfonic acid (1.5 mL)and dichloromethane (3.5 ml) was added solid sodium azide (1.52 g, 8.0mmol). To that mixture was added the hydroxylated tetramantanes (2) asprepared in Example 2 above. To this resulting mixture was added insmall increments sodium azide (1.04 g, 16 mmol) over a period of about0.5 h. Stirring was continued for about 8 h at 20-25° C., and then themixture was poured into ice water (ca. 10 ml). The aqueous layer wasseparated, washed with CH₂Cl₂ (3 mL), basified with 50% aqueous KOH-ice,and extracted with CH₂Cl₂ (10 mL×4). The combined extracts were driedwith Na₂SO₄, and the solvent was removed to afford a brownish oilproduct. The product was characterized by GC/MS to show the presence ofazahomo tetramantane-ene isomers (14). The chromatograms and massspectra showing the azahomo molecules are shown in FIGS. 42-46.

In the next step, an epoxy azahomo tetramantane was made from theazahomo tetramantane-enes. The above mixture was treated with m-CPBA(1.1 eq.) in CH₂Cl₂—NaHCO₃ at a temperature of about 20° C. for about 12h, and the reaction mixture was then worked up with a CH₂Cl₂ extractionto afford a crude product that was characterized by GC/MS (FIGS. 47-51)to show the presence of epoxy azahomo tetramantane.

In the next step, a mixture of N-formyl aza tetramantanes was preparedfrom the epoxy azahomo tetramantane mixture by irradiating the epoxy azatetramantane mixture in cyclohexane using a high intensity Hg lamp forabout 0.5 hours. The reaction was carried out in an argon atmosphere.Generally speaking, a simpler reaction product was obtained if thereaction was allowed to proceed for only a short time; longer periodsgave a complex mixture. The initial product was characterized by GC/MS(FIGS. 52-56) as a mixture of N-formyl aza tetramantanes.

In a final step, aza tetramantanes were prepared from the abovedescribed N-formyl aza tetramantanes by mixing the N-formyl azatetramantanes with 10 mL of 15% hydrochloric acid. The resultant mixturewas heated to a boil for about 24 hours. After cooling, the mixture wassubjected to a typical workup to afford a product which wascharacterized by GC/MS (FIGS. 57-63) showing the presence of azatetramantanes.

Example 4 Oxidation of Hydroxylated Compound 2 to Keto Compound 1

Photohydroxylated iso-tetramantane containing a mixture of C-2 and C-3hydroxylated iso-tetramantanes dissolved in acetone is prepared as setout in Example 2. The oxygenated components go into the solution but notall of the unreacted iso-tetramantane. Chromic acid-sulfuric acidsolution is added dropwise to the solution until an excess is present,and the reaction mixture is stirred overnight. The acetone solution isdecanted from the precipitated chromic sulfate and the unreactediso-tetramantane, and is dried with sodium sulfate. The unreactediso-tetramantane is recovered by dissolving the chromium salts in waterand filtering. Evaporation of the acetone solution affords a whitesolid. This crude solid is chromatographed on alumina with standardprocedures eluting first with 1:1 (v/v) benzene/light petroleum etherfollowed by ethyl ether or a mixture of ethyl ether and methanol (95:5v/v) to collect the unreacted iso-tetramantane and the keto compound 1(FIG. 3), respectively. Further purification by recrystallization fromcyclohexane affords a pure product 1.

Alternatively, iso-tetramantane is directly oxidized to keto compound 1according to the procedures of McKervey et al. (J. Chem. Soc., PerkinTrans. 1, 1972, 2691).

Reduction of Keto Compound 1 to C-2 Hydroxylated Iso-Tetramantane 2a

As shown in FIG. 3, the keto compound 1 is reduced with lithium aluminumhydride (a little excess) in ethyl ether at low temperatures to prepareC-2 hydroxylated iso-tetramantane 2a. After completion of the reaction,the reaction mixture is worked up by adding saturated Na₂SO₄ aqueoussolution to decompose excess hydride at low temperature. Decantationfrom the precipitated salts gives a dry ether solution, which, whenevaporated, affords a crude monohydroxylated iso-tetramantanesubstituted at the secondary carbon, i.e. C-2 tetramantan-ol which ispurified by recrystallization from cyclohexane.

C-2 Methyl Hydroxyl Iso-Tetramantane 2b from Keto Compound 1

Alternatively, as shown in FIG. 3, to a stirred solution of ketocompound 1 (2 mmol) in dry THF (20 mL) at −78° C. (dry ice/methanol) isadded dropwise a 0.8 molar solution (2.8 mL, 2.24 mmol) of methyllithiumin ether. Stirring is continued for about 2 h at −78° C. and for anotherabout 1 h at room temperature. Then, saturated ammonium chloridesolution (1 mL) is added, and the mixture extracted with ether (2×30mL). The organic layer is dried with sodium sulfate and concentrated togive the product 2b which is subjected to further purification by eitherchromatography or recrystallization.

Oxa Iso-Tetramantane 3 from C-2 Hydroxylated Iso-Tetramantane 2a

A solution of C-2 hydroxylated iso-tetramantane 2a (1.32 mmol) in drybenzene (60 mL) containing mercury(II) oxide (850 mg) and iodine (1.006g) is irradiated for about 7 h in an atmosphere of nitrogen by theprocedure reported by Suginome et al. (J. Org. Chem., 1984, 49, 3753).Work-up as reported gives a product which is subjected to preparativeTLC on silica gel benzene/ether to give the product 3, as well as someamount of lactone 4 and the starting material 2a.

Oxa Iso-Tetramantane 3 from C-2 Methyl Hydroxylated Iso-Tetramantane 2b

A solution of C-2 methyl hydroxyl iso-tetramantane 2b (0.6 mmol) in drybenzene (30 mL) containing mercury(II) oxide (392 mg) and iodine (459mg) is irradiated for about 3 h in an atmosphere of nitrogen by theabove procedure. Work-up of the solution gives a product which issubjected to preparative TLC on silica gel with benzene/ether to givethe product 3.

Oxa Iso-Tetramantane 3 from C-2 Methyl Hydroxyl Iso-Tetramantane 2b

C-2 methyl hydroxyl iso-tetramantane 2b (6.02 mmol) is added to asolution of TFPAA (trifluoroperacetic acid) in TFAA (trifluoroaceticacid) (13 g, 48.5 mmol) at 0° C. After being stirred for about 15 min.at 0° C., the reaction mixture is allowed to warm to r.t., stirring forabout 1 h, and then poured into a solution of 15% NaOH (50 mL) with ice.The mixture is extracted with CH₂Cl₂ (3×15 mL). The combined extract isthen washed with water and 5% aqueous Na₂SO₃. The organic layer is driedover Na₂SO₄ and the solvent evaporated. The residue is separated on asilica column eluting with a mixture of hexane-ether to afford thepreduct oxa iso-tetramantane 3.

Example 5 Preparation of Lactone 4

Lactone 4 of FIG. 4 is prepared according to the general procedure of[Udding et al., Tetrahedron Lett., 1968, 5719].

Preparation of Compound 5a from Compound 4

To a solution of lactone 4 (4.5 mmol) in dry toluene (80 mL) at −78° C.(cooled by dry ice/methanol) is added dropwise diisobutylaluminiumhydride (20% in hexane, 5 mL) over a period of 20 min. The solution isstirred for 2 h at −78° C. and then poured into ice water. After removalof the precipitates, the solution is washed with water (1×50 mL) anddried with sodium sulfate. The solvent is evaporated to give the crudelactol 5a, which is recrystallized from hexane for further purification.

Preparation of Compound 5b from Compound 4

To a stirred solution of lactone 4 (2 mmol) in dry tetrahydrofuran (THF)(20 mL) at −78° C. (dry ice/methanol) is added dropwise a 0.8 molarsolution (2.8 mL, 2.24 mmol) of methyllithium in ether. Stirring iscontinued for about 2 h at −78° C. and for about 1 h at roomtemperature. Then, saturated ammonium chloride solution (1 mL) is added,and the mixture extracted with ether (2×30 mL). The organic layer isdried with sodium sulfate and concentrated to give the crystallineproduct 5b which is recrystallized from petroleum ether for furtherpurification.

Preparation of Compound 6a by Irradiation of 5a

To a solution of lactol 5a (1.2 mmol) in dry benzene (60 mL) containingpyridine (0.5 mL) is added mercury(II) oxide (520 mg) and iodine (610mg). The solution is placed in a Pyrex vessel, flushed with nitrogen,and irradiated by a 100-W high-pressure mercury arc. The irradiation isdiscontinued after about 2 h. The solution is then washed with aqueous5% sodium thiosulfate solution (30 mL), water (50 mL), and saturatedsodium chloride solution (50 mL) and is dried with sodium sulfate. Thesolvent is evaporated to give the crude product 6a. Preparative TLC ofthis product with benzene affords two fractions A and B in the order ofdecreasing mobility. Fraction A is product 6a while fraction B islactone 4.

Preparation of Compound 6b from 5b

To a solution of lactol 5b (1.2 mmol) in dry benzene (55 mL) containingpyridine (1 mL) are added mercury(II) oxide (477 mg) and iodine (588mg). The solution is photolyzed as in the case of lactol 5a to give acrude product. The product is subjected to preparative TLC with benzeneto give product 6b.

Example 6 Fragmentation of Keto Compound 1 to Unsaturated CarboxylicAcid 9 of FIG. 5

Fragmentation of iso-tetramantone 1 as prepared above to the unsaturatedcarboxylic acid 9 by an abnormal Schmidt reaction likewise followsMcKervey et al. (Synth. Commun., 1973, 3, 435) and is analogous to thebehavior reported for adamantane and diamantane (Sasaki et al., J. Org.Chem., 1970, 35, 4109; Fort, Jr. et al., J. Org. Chem., 1981, 46(7),1388).

Preparation of Compound 10 (Exo- and Endo) from Acid 9

To 4.6 mmol of the carboxylic acid 9 are added 12 mL of glacial aceticacid and 3.67 g (4.48 mmol) of anhydrous sodium acetate. The mixture isstirred and heated to about 70° C. Lead(IV) acetate (3.0 g, 6.0 mmol,90% pure, 4% acetic acid) is added in three portions over 30 min.Stirring is continued for 45 min at 70° C. The mixture is then cooleddown to room temperature and diluted with 20 mL of water. The resultingsuspension is stirred with 20 mL of ether, and a few drops of hydrazinehydrate are added to the dissolve the precipitated lead dioxide. Theether layer then is separated, washed several times with water and oncewith saturated sodium bicarbonate, and dried over anhydrous sodiumsulfate. Removal of the ether gives an oily material from which amixture of the two isomers (exo- and endo-) of compound 10 is obtained.Further purification and separation of the stereochemical isomers (exo-and endo-) can be achieved by distillation under vacuum.

Preparation of Compound 11 (Exo- or Endo) from Compound 10 (Exo- orEndo)

To a solution of compound 10 (0.862 mmol) in 5 mL of anhydrous ether isadded 0.13 g (3.4 mmol) of lithium aluminum hydride, and the mixture isrefluxed with stirring for about 24 h. The excess lithium aluminumhydride is destroyed by addition of water dropwise, and the precipitatedlithium and aluminum hydroxides are dissolved in excess 10% hydrochloricacid. The ether layer is separated, washed with water, dried overanhydrous sodium sulfate, and evaporated to give compound 11 (mixturesof exo-11 and endo-11 isomers if using mixtures of exo-10 and endo-10).Further purification can be achieved by recrystallization frommethanol-water.

Preparation of Compound 12 from Compound 11 (Exo- and Endo-Mixture)

A solution of a mixture of the alcohols 11 (1.05 mmol) in 5 mL ofacetone is stirred in an Erlenmeyer flask at 25° C. To this solution isadded dropwise 8 N chromic acid until the orange color persists, thetemperature being kept at 25° C. The orange solution is then stirred at25° C. for about additional 3 h. Most of the acetone is removed, and 5mL of water is added to the residue. The aqueous mixture is extractedtwice with ether, and the combined extracts are washed with saturatedsodium bicarbonate, dried over anhydrous sodium sulfate, and evaporatedto give crude 12. Sublimation on a steam bath gives pure 12.

Preparation of Compound 12 from Exo-11

A solution of exo-11 (1.05 mmol) in 5 mL of acetone is stirred in anErlenmeyer flask at 25° C. To this solution is added dropwise 8 Nchromic acid until the orange color persisted, the temperature beingkept at 25° C. The orange solution is then stirred at 25° C. for aboutadditional 3 h. Most of the acetone is removed, and 5 mL of water isadded to the residue. The aqueous mixture is extracted twice with ether,and the combined extracts are washed with saturated sodium bicarbonate,dried over anhydrous sodium sulfate, and evaporated to give crude 12.Sublimation on a steam bath gives pure 12.

Preparation of Compound 12 from Acid 9

A solution of the carboxylic acid 9 (4.59 mmol) in 15 mL of dry THF isstirred under dry argon and cooled to 0° C. A solution of 1.5 g (13.76mmol) of lithium diisopropylamide in 25 mL of dry THF under argon isadded through a syringe to the solution of 9 at such a rate that thetemperature does not rise above 10° C. The resulting solution of thedianion of 9 is stirred at 0° C. for about 3 h. It is then cooled to−78° C. with a dry ice-acetone bath, and dry oxygen is bubbled slowlythrough the solution for about 3 more. A mixture of about 10 mL of THFand 1 mL water is added to the reaction mixture, which is then allowedto warm to room temperature and is stirred overnight. The solution isconcentrated to about 10 mL at water pump pressure, poured into excess10% HCl, and extracted with ether. The ether layer is washed with 5%NaOH to remove unreacted 9, which is recovered by acidification of thebasic wash. The ether layer is dried over anhydrous sulfate and strippedto yield crude 9. Sublimation on a steam bath at 3-5 torr gives pureproduct.

Preparation of Endo-11 from Compound 12

To a solution of ketone 12 (0.9 mmol) in 5 mL of anhydrous ether isadded 0.13 g (3.4 mmol) of lithium aluminum hydride, and the mixture isstirred and refluxed for about 24 h. The excess lithium aluminum hydrideis destroyed by dropwise addition of water, and the precipitated lithiumand aluminum hydroxides are dissolved in excess 10% HCl. The ether layeris separated and dried over anhydrous sodium sulfate. Removal of thesolvent gives the crude but stereochemically pure endo-11, which isfurther purified by sublimation on a steam bath under water pumppressure.

Oxa Iso-Tetramantane 3 from Endo-11

To endo-11 (1.58 mmol) is added 25 mL of 50% sulfuric acid, and thesolution is stirred vigorously at room temperature for about 24 h. Thereaction mixture is then poured onto 100 g ice and the mixture extractedtwice with ether. The ether extract is dried over anhydrous sodiumsulfate and evaporated. The crude product is purified by sublimation ona steam bath at water pump pressure.

Example 7 Oxa Iso-Tetramantane 3 from 6a or 6b with Methyllithium asShown in FIG. 4

To a stirred solution of compound 6a (0.19 mmol) in dry THF (5 mL), a0.8 molar solution (0.52 mL, 0.424 mmol) of methyllithium in ether isadded dropwise at −78° C. Stirring is continued for about 1 h at −78° C.and for about another 1 h at room temperature. Water (10 mL) is thenadded and the mixture is extracted with ether (2×20 mL). The organiclayer is washed with water (20 mL) and saturated sodium chloridesolution (20 mL) and is dried with sodium sulfate. The solvent isevaporated to give crystals. The product is further purified bypreparative TLC on silica gel using mixtures of benzene and ether.

Oxa Iso-Tetramantane 3 from 6a by Column Chromatography on Silica Gel

Compound 6a (0.09 mmol) in dichloromethane (1 mL) is adsorbed on acolumn of silica gel for about 24 h. Elution of the column withdichloromethane gives the product 3 and some starting compound 6a.

Oxa Iso-Tetramantane 3 from 6a Thermally

Compound 6a (0.09 mmol) is heated at 60° C. for about 30 min., and thensubjected to preparative TLC with benzene/ether to yield the product 3and the starting material 6a.

Example 8 Preparation of Thia-Iso-Tetramantane Starting fromIso-Tetramantone 6b of FIG. 6 Preparation of Compound 7 from 6b

Compound 6b is prepared as described in a previous example. To asolution of compound 6b (0.78 mmol) in dry carbon tetrachloride (4 mL)is added to iodotrimethylsilane (312 mg, 1.56 mmol) at room temperatureand the mixture is stirred for about 4 h. Water (20 mL) is then addedand the mixture is extracted with ether (2×30 mL). The organic extractis washed with 5% sodium thiasulfate (20 mL), water, and saturatedsodium chloride solution (30 mL) and is dried with sodium sulfate. Thesolvent is evaporated to give the crystalline product 7, whichdecomposes upon heating above about 90° C.

Preparation of Thia Iso-Tetramantane 8 from Compound 7

Compound 7 (1 mmol) is dissolved in ethanol (10 mL) by warming Sodiumsulfide (Na₂S.9H₂O, 950 mg, 3.96 mmol) is added and the mixture isrefluxed for about 10 h. Then, water (30 mL) is added and the mixture isextracted with ether (2×30 mL). The organic extract is washed with water(40 mL) and with saturated sodium chloride solution (40 mL) and is driedwith sodium sulfate. The solvent is evaporated to give crystalline thiaiso-tetramantane 8 which is further purified by preparative TLC onsilica gel (hexane/benzene).

Example 9 Preparation of Compound 13 from Compound 12 (FIG. 6)

Compound 12 is prepared as described in a previous example starting fromiso-tetramantone 1. Hydrogen sulfide is passed continuously for 2 daysthrough a solution of compound 12 (1.06 mmol) in 15 mL of absoluteethanol. The solution is kept acidic by passing hydrogen chloride duringevery other 12-h period. The reaction mixture is kept at 0° C. duringthe passage of the gases. The resulting orange solution is extractedwith 50 mL of ether in portions. The ether extracts are washed twicewith water, dried over anhydrous sodium sulfate, and stripped to yieldan orange semisolid. No further purification is needed and the materialis used directly in the following reaction.

Thia Iso-Tetramantane 8 from Compound 13

The crude compound 13 is dissolved in 100 mL of anhydrous ether, and 500mg (13.16 mmol) of lithium aluminum hydride is added. The mixture isstirred at reflux for about 2 days. Excess lithium aluminum hydride isdestroyed with water, and the precipitated lithium and aluminumhydroxides are dissolved in excess 10% HCl. The layers are separated,and the aqueous phase is extracted with 50 mL of ether. The combinedether extracts are dried over anhydrous sodium sulfate and stripped.Sublimation of the residue on a steam bath at water pump pressure givesthe product 8 contaminated with a small amount of endo-11. This mixtureis chromatographed on neutral alumina. Elution with hexane gives pure 8;subsequent elution with ether gives endo-11. Further purification of 8is by sublimation on a steam bath at water pump pressure.

Example 10 Preparation of Aza Iso-Tetramantane from Iso-Tetramantane(FIGS. 7 & 8)

In this example, an aza iso-tetramantane is prepared from a singletetramantane isomer, iso-tetramantane, as shown in FIGS. 7-8. As withthe reactions using a mixture of tetramantanes shown in Example 2, thissynthetic pathway begins with the photo-hydroxylation ofiso-tetramantane using the method of Example 2 or chemicaloxidation/reduction to the hydroxylated compound 2a shown in FIG. 7.

This photo-hydroxylated iso-tetramantane containing a mixture of C-2 andC-3 hydroxylated iso-tetramantanes is converted to keto compound 1 viathe process set out in Example 4.

In the next step, the azahomo iso-tetramantane-ene 14 is prepared fromthe hydroxylated compound 2 using the general method set out in Example3.

In the next step, an epoxy azahomo iso-tetramantane 15 is prepared alsoas shown in Example 3.

In the next step, N-acyl aza iso-tetramantane 16b is prepared from theepoxy azahomo iso-tetramantane 15b by irradiating the epoxy azahomoiso-tetramantane 15b in cyclohexane for about 0.5 hours with a UV lamp.The radiation passes through a quartz filter and the reaction is carriedout under an argon atmosphere. Generally speaking, a single product isformed when the reaction is allowed to proceed for only a short time:longer periods gives a complex mixture of products. Products may beisolated by chromatographic techniques.

N-formyl aza iso-tetramantane 16a can be similarly prepared from theepoxy azahomo iso-tetramantane 15a.

In the next step, the aza iso-tetramantane 17 is prepared from N-acylaza-isotetramantane 16b by heating the N-acyl aza iso-tetramantane 16b(5 mmol) to reflux for about 5 hours with a solution of 2 g powderedsodium hydroxide in 20 mL diethylene glycol. After cooling, the mixtureis poured into 50 mL water and extracted with ethyl ether. The etherextract is dried with potassium hydroxide. The ether is distilled off toafford the product aza iso-tetramantane 17. The hydrochloride salt isgenerally prepared for analysis. Thus, dry hydrogen chloride is passedinto the ether solution of the amine, whereby the salt separates out asa crystalline compound. The salt may be purified by dissolving it inethanol, and precipitating with absolute ether. Typically, the solutionis left undisturbed for several days to obtain complete crystallization.

Alternatively, the aza iso-tetramantane 17 may be prepared from theN-formyl aza iso-tetramantane 16a by mixing the N-formyl azaiso-tetramantane 16a (2.3 mmol) with 10 mL of 15% hydrochloric acid asshown in Example 3.

Example 11 Preparation of the Aza Iso-Tetramantane 17 by Fragmentationof a Keto Compound 1 (FIG. 8)

To a solution of compound 12 (FIG. 5) (1.6 mmol) in a mixture ofpyridine and 95% ethanol (1:1) is added 250 mg (3.6 mmol) ofhydroxylamine hydrochloride, and the mixture is stirred at reflux forabout 3 days. Most of the solvent is evaporated in a stream of air, andthe residue is taken up in 25 mL of water. An ether extract of theaqueous solution is washed with 10% HCl to extract the oxime 18.Neutralization of the acid wash with 10% sodium hydroxide precipitatesthe oxime 18, which is filtered off and recrystallized fromethanol-water.

In a final step, the aza iso-tetramantane 17 is prepared from compound18 by the dropwise addition of a solution of compound 18 (0.98 mmol) in25 mL of anhydrous ether to a stirred suspension of 250 mg (6.58 mmol)of lithium aluminum hydride in 25 mL of anhydrous ether. The mixture isstirred at reflux for about 2 days. Excess lithium aluminum hydride isdestroyed with water, and the precipitated lithium and aluminumhydroxides are dissolved in excess 25% sodium hydroxide. The resultingbasic solution is extracted twice with ether, and the combined extractsare then washed with 10% HCl. Neutralization of the acidic wash with 10%sodium hydroxide precipitates product 6, which is extracted back intofresh ether. The ether solution is dried over anhydrous sodium sulfateand stripped. The crude product is purified by repeated sublimation on asteam bath under vacuum.

Example 12 Monobromination of Heterodiamondoids

As shown in FIG. 13, a heterodiamondoid (7.4 mmol) is mixed withanhydrous bromine (74 mmol) in a 150 mL round bottom flask. Whilestirring, the mixture is heated in an oil bath for about 4.5 h, wherebythe temperature is gradually raised from an initial 30° C. to 105° C.After cooling, the product monobrominated heterodiamondoid dissolved inexcess bromine is taken up with 100 mL carbon tetrachloride and pouredinto 300 mL ice water. The excess bromine is then removed with sodiumhydrogen sulfide while cooling with ice water. After the organic phasehas been separated, the aqueous solution is extracted once more withcarbon tetrachloride. The combined extracts are washed three times withwater. After the organic phase has been dried with calcium chloride, thesolvent is distilled off and the last residues are removed under vacuum.The residue is dissolved in a small amount of methanol and crystallizedin a cold bath. Further purification of the crystals is carried out bysublimation under vacuum.

Example 13 Dibromination of Heterodiamondoids without Catalysts

As shown in FIG. 13, a heterodiamondoid (37 mmol) is heated to 150° C.for about 22 h with anhydrous bromine (0.37 mol) in a pressure vessel.Usual work-up and recrystallization of the reaction product frommethanol is performed as described above. The crystals are sublimated invacuum. The sublimate is recrystallized several times from a very smallamount of n-hexane affording a dibrominated derivative.

Example 14 Brominated Heterodiamondoids from Hydroxylated Compounds(FIG. 13)

A mixture of a suitable hydroxylated heterodiamondoid and excess 48%hydrobromic acid is heated to reflux for a few hours (which can beconveniently monitored by GC analysis), cooled, and extracted with ethylether. The extract is combined and washed with aqueous 5% sodiumhydroxide and water, and dried. Evaporation and normal columnchromatography on alumina eluting with light petroleum ether, hexane, orcyclohexane or their mixtures with ethyl ether affords the bromide withreasonable high yields.

Example 15 G-CH₂CH₂—Br from G-Br

A solution of a suitable monobrominated heterodiamondoid G-Br (0.046mole) in 15 mL n-hexane in a 150-mL three-necked flask equipped with astirrer, a gas inlet tube and a gas discharge tube with a bubble counteris cooled to −20 to −25° C. in a cooling bath. While stirring oneintroduces 4.0 g powdered freshly pulverized aluminum bromide of highquality, and ethylene is conducted in such a way that the gas intake canbe controlled with the bubble counter. The reaction starts with a slightdarkening of the color and is completed after about 1 h. The reactionsolution is decanted from the catalyst into a mixture of ether andwater. The ether layer is separated off, and the aqueous phase isextracted once more with ether. The combined ether extracts are washedwith water and dilute sodium carbonate aqueous solution. After they havebeen dried over calcium chloride, the solvent is distilled off.Recrystallizing from methanol affords the pure heterodiamondoid ethylbromide G-CH₂CH₂—Br.

Example 16 G-CH═CH—Br from G-Br

Step 1: in a 150-mL two-necked flask with a stirrer and a drying tube, amixture of 0.069 mole of a suitable monobromonated heterodiamondoid G-Brand 20 mL vinyl bromide is cooled to −65° C. in a cooling bath. Whilestirring, 4.5 g powdered aluminum bromide is added in portions and themixture is stirred for an additional about 3 hours at the sametemperature. Then the reaction mixture is poured into a mixture of 30 mLwater and 30 mL ethyl ether. After vigorously stirring, the ether layeris separated and the aqueous layer is extracted once more with ether.The combined ether extracts are washed with water and dilute sodiumcarbonate solution. After it has been dried with calcium chloride andthe solvent has been distilled off, the residue is distilled undervacuum.

Step 2: a solution of 0.7 g fine powdered potassium hydroxide and theabove compound (0.012 mole) in 10 mL diethylene glycol is heated to 220°C. in the oil bath for 6 hours. After cooling down the mixture isdiluted with 30 mL water and exacted with ethyl ether. The ether extractis washed twice with water and dried over calcium chloride. The residueleft behind after the ether has been distilled off is sublimated invacuum, and if necessary, the compound can be recrystallized frommethanol.

G-CC≡Br can also be formed from G-Br using this method and appropriatestarting materials.

Example 17 G-C₆H₄—Br from G-Br

1.1 g sublimated iron(III) chloride and high pure C₆H₅Br (excess) areplaced in a 150-mL three-necked flask, which is equipped with a stirrer,a reflux condenser and a dropping funnel. While stirring and heating inthe steam bath, a suitable monobrominated heterodiamondoid G-Br (0.018mole) is slowly added to the above flask over about 30 minutes. Thereaction mixture is heated for about an additional 3 hours until theproduction of hydrogen bromide drops off. The mixture is kept standingover night and poured onto a mixture of ice and hydrochloric acid. Theorganic phase is separated out and the aqueous solution is extractedtwice with benzene. The combined benzene extracts are washed severaltimes with water and dried with calcium chloride. The residue solidifiesupon cooling and is completely free of the solvent in vacuum.Recrystallization from a small amount of methanol while cooling withCO₂/trichloroethylene and further sublimation under vacuum afford a pureproduct.

Example 18 Monochlorination of Heterodiamondoids

A solution of 0.074 mole of a heterodiamondoid and 10 mL (8.5 g, 0.092mole) of tert-butyl chloride in 40 mL of anhydrous cyclohexane isprepared in a 0.1 L, three-necked, round-bottom flask fitted with athermometer, a stirrer, and a gas exhaust tube leading to a bubblersubmerged in water. The catalyst, aluminum chloride (total 0.46 g, 0.006mole) is added in batches of 0.05 g at regular intervals over a periodof about 8 hours. Progress of the reaction is followed conveniently bythe rate of escaping isobutane gas. Upon completion of the reaction, 10mL of 1.0 N hydrochloride acid solution is added with vigorous stirring,followed by 50 mL of ethyl ether. The organic layer is separated, washedwith 10 mL of cold water and 10 mL of a 5% sodium bicarbonate solution,and dried over anhydrous calcium chloride. After removal of the solventsunder reduced pressure, the crude product is obtained. GC analysis ofthis material reveals a composition of mainly monochlorinatedheterodiamondoid with a small amount of unreacted heterodiamondoid. Ifnecessary, recrystallization of a sample of this material from ethanolat −50° C. affords a pure monochlorinated heterodiamondoid.

Example 19 Monohydroxylation of Heterodiamondoids

A solution of 11.0 mmol of a heterodiamondoid in 18.7 g of methylenechloride is mixed with 4.22 g of a solution of 1.03 g (13.5 mmol) ofperacetic acid in ethyl acetate. While being stirred vigorously, thesolution is irradiated with a 100-watt UV light placed in an immersionwell in the center of the solution. Gas evolution is evident from thestart. The temperature is maintained at 40-45° C. for an about 21-hourirradiation period. At the end of this time, about 95% of the peracidhad been consumed. The solution is concentrated to near dryness, treatedtwice in succession with 100-mL portions of toluene and reevaporated todryness. Final drying in a desiccator affords a white solid. A portionof the above material is dissolved in a minimum amount of benzene-lightpetroleum ether. This solution is then subjected to chromatography onalumina in the usual manner eluting with firstly 1:1 benzene/lightpetroleum ether, followed by a mixture of methanol and ethyl ether tocollect the unreacted heterodiamondoid, and the hydroxylatedheterodiamondoid isomers, respectively. Further separation of theisomers can be achieved by using HPLC technique.

Example 20 Polyhydroxylation of Heterodiamondoids

Into a 4-neck flask immersed in a cooling bath and equipped with a lowtemperature condenser (−20° C.), and an air driven, well sealedmechanical stirrer, a solid addition funnel and a thermocouple, is added0.037 mole of a heterodiamondoid, 150 mL methylene chloride, 200 mLdouble distilled water, 192 grams sodium bicarbonate and 300 mLt-butanol. The mixture is stirred and cooled to 0° C. and 200 grams1,1,1-trifluoro-2-propanone (TFP) are added. The mixture is stirred andcooled down to ±8° C. 200 grams oxone are added from the solid additionfunnel over the course of 3 hours. The reaction mixture is stirred at 0°C. overnight (16 hours). The TFP is recovered by distillation (heatingpot to 40° C. and condensing TFP in a receiver immersed in dryice/acetone). The remainder mixture is filtered by suction and a clearsolution is obtained. The solution is rotavapped to dryness, providing amixture of polyhydroxylated heterodiamondoids that are purified bychromatography and/or recrystallization.

Example 21 Monohydroxylated Heterodiamondoids from MonobrominatedCompounds (FIG. 15)

A suitable monobrominated heterodiamondoid (0.066 mol) is heated toreflux for about 1 h in a round bottom flask, which is equipped with astirrer and a reflux condenser, while stirring and adding 35 mL water,3.5 mL tetrahydrofuran, 2.0 g potassium carbonate and 1.3 g silvernitrate. After cooling, the reaction product, which has crystallizedout, is separated out and is extracted with tetrahydrofuran. The extractis diluted with water and the precipitate is suctioned off, dried andpurified by sublimation under vacuum.

Example 22 G-CH₂CH₂—OH from G-CH₂CH₂Br (FIG. 15)

A suitable G-CH₂CH₂—Br (0.066 mol) is heated to reflux for about 1 h ina round bottom flask, which is equipped with a stirrer and a refluxcondenser, while stirring and adding 35 mL water, 3.5 mLtetrahydrofuran, 2.0 g potassium carbonate and 1.3 g silver nitrate.After cooling, the reaction product is separated out and is extractedwith chloroform. Evaporating the solvent affords the product afterpurification by column chromatography.

Example 23

C-2 G-OH from G=O (FIG. 15)

A suitable hetero diamondoidone G=O is reduced with lithium aluminumhydride (a little excess) in ethyl ether at low temperatures. Aftercompletion of the reaction, the reaction mixture is worked up by addingsaturated Na₂SO₄ aqueous solution to decompose excess hydride at lowtemperature. Decantation from the precipitated salts gives a dry ethersolution, which, when evaporated, affords a crude C-2 monohydroxylatedheterodiamondoid substituted at the secondary carbon, i.e. C-2 G-OH.Further recrystallization from cyclohexane gives an analytically puresample.

Example 24 Diesterified Heterodiamondoids from Dihydroxylated Compounds

To 2 mL of dioxane is added a dihydroxylated heterodiamondoid (1.0 mmol)and triethylamine (2.2 mmol) at a temperature of 50° C. The resultantmixture is added dropwise to a solution of acrylic acid chloride (2.2mmol) in dioxane (2 mL). The mixture is maintained at 50° C. for about 1hour. The product is analyzed by GC. When the analysis confirms theformation of the desired diacrylate, the compound is isolated usingstandard methods.

Example 25 Oxidation of Heterodiamondoids to Heterodiamondoidones

A solution of 11.0 mmol of a suitable heterodiamondoid in 18.7 g ofmethylene chloride is mixed with 4.22 g of a solution of 1.03 g (13.5mmol) of peracetic acid in ethyl acetate. While being stirredvigorously, the solution is irradiated with a 100-watt UV light placedin an immersion well in the center of the solution. Gas evolution isevident from the start. The temperature is maintained at 40-45° C. foran about 21-hour irradiation period. At the end of this time, about 95%of the peracid had been consumed. The solution is concentrated to neardryness, treated twice in succession with 100-mL portions of toluene andreevaporated to dryness. Final drying in a desiccator affords a crudewhite solid.

The crude hydroxylated heterodiamondoid mixture is then partiallydissolved in acetone. The oxygenated components go into the solution butnot all of the unreacted heterodiamondoid. Chromic acid-sulfuric acidsolution is added dropwise until an excess is present, and the reactionmixture is stirred overnight. The acetone solution is decanted from theprecipitated chromic sulfate and the unreacted heterodiamondoid, and isdried with sodium sulfate. The unreacted heterodiamondoid is recoveredby dissolving the chromium salts in water and filtering. Evaporation ofthe acetone solution affords a white solid. This crude solid ischromatographed on alumina with standard procedures eluting first with1:1 (v/v) benzene/light petroleum ether followed by ethyl ether or amixture of ethyl ether and methanol (95:5 v/v) to collect the unreactedheterodiamondoid and the heterodiamondoidone, respectively. Furtherpurification by recrystallization from cyclohexane affords a pureheterodiamondoidone.

Example 26 2,2-Bis(4-hydroxyphenyl)Heterodiamondoids from Keto Compounds

A flask is charged with a mixture of a heterodiamondoidone (0.026 mole),phenol (16.4 g, 0.17 mole), and butanethiol (0.15 mL). Heat is appliedand when the reaction mixture becomes liquid at about 58° C., anhydroushydrogen chloride is introduced until the solution becomes saturated.Stirring is continued at about 60° C. for several hours, during whichperiod a white solid begins to separate out from the reddish-orangereaction mixture. The solid obtained is filtered off, washed withdichloromethane and dried to afford the bisphenol heterodiamondoidproduct. It is purified by sublimation after recrystallization fromtoluene.

Example 27 2,2-Bis(4-aminophenyl)Heterodiamondoids from Keto Compounds

To a solution of a heterodiamondoidone (0.041 mole) in 15 mL of 35% HClaqueous solution in a 100 mL autoclave equipped with a stirrer is addedexcess aniline (15.7 g, 0.17 mole) and the mixture is stirred at about120° C. for about 20 hours. After cooling, the solution is made basicwith NaOH aqueous solution to pH 10 and the oily layer is separated anddistilled to remove the unreacted excess aniline. The residual crudeproduct is recrystallized from benzene.

Example 28 2,2-Bis[4-(4-aminophenoxy)phenyl]Heterodiamondoids fromBisphenol Heterodiamondoids

A mixture of a 2,2-bis(4-hydroxyphenyl)heterodiamondoid (0.01 mole),p-fluoronitrobenzene (3.1 g, 0.022 mole), potassium carbonate (3.31 g,0.024 mole) and N,N,-dimethylacetamide (DMAc, 10 mL) is refluxed forabout 8 hours. The mixture is then cooled and poured into aethanol/water mixture (1:1 by volume). The crude product is crystallizedfrom DMF to provide yellow needles of the2,2-bis[4-(4-nitrophenoxy)phenyl]heterodiamondoid.

Hydrazine monohydrate (20 mL) is added dropwise to a mixture of theabove product (0.002 mole), ethanol (60 mL), and a catalytic amount of10% palladium on activated carbon (Pd/C, 0.05 g) at the boilingtemperature. The reaction mixture is refluxed for about 24 hours, andthe product 2,2-Bis[4-(4-aminophenoxy)phenyl]heterodiamondoid isprecipitated during this period. The mixture is then added to enoughethanol to dissolve the product and filtered to remove Pd/C. Aftercooling, the precipitated crystals are isolated by filtration andrecrystallized from 1,2-dichlorobenzene.

Example 29 Mononitration of Heterodiamondoids

A mixture of 0.05 mole of a heterodiamondoid and 50 mL of glacial aceticacid is charged to a stirred stainless 100 mL autoclave which ispressurized with nitrogen to a total pressure of 500 p.s.i.ga. After themixture is then heated to 140° C., 9.0 g (0.1 mole) of concentratednitric acid is introduced into the reaction zone by means of a feed pumpat a rate of 1-2 mL per minute. When the acid feed is completed, thereaction temperature is maintained at 140° C. for 15 minutes, afterwhich time the reaction mixture is cooled down to room temperature anddiluted with an excess of water to precipitate the products. Thefiltered solids are slurried with a mixture of 10 mL of methanol, 15 mLof water, and 1.7 g of potassium hydroxide for 18 hours at roomtemperature. After dilution with water, the alkali-insoluble material isextracted by light petroleum ether. The petroleum ether extracts arewashed by water and dried over anhydrous magnesium sulfate.Concentration of this solution affords a white solid. The aqueous alkalisolution from which the alkali-insoluble material had been extracted iscooled to 0-3° C. and neutralized by the dropwise addition of an aqueousacetic acid-urea mixture to regenerate some more products. GC analysisshows that the alkali-insoluble sample is mainly mononitroheterodiamondoid.

Example 30 Monocarboxylation of Heterodiamondoids

A mixture of 29.6 g (0.4 mole) tert-butanol and 55 g (1.2 mole) 99%formic acid is added dropwise over about 3 hours to a mixture of 470 g96% sulfuric acid and 0.1 mole heterodiamondoid dissolved in 100 mLcyclohexane while stirring vigorously at room temperature. Afterdecomposing with ice, the acids are isolated and purified byrecrystallization from methanol/water giving the monocarboxylatedheterodiamondoid.

Example 31 G-CHClCOOH from G-Br

A mixture of a suitable monobrominated heterodiamondoid G-Br (0.012mole) and 9.0 g trichloroethylene CHCl═CCl₂ is added dropwise in thecourse of about 4 hours into 24 mL 90% sulfuric acid at 103-106° C.while stirring. After the addition is completed, the mixture is stirredfor about an additional 2 hours at the specified temperature, thencooled down and hydrolyzed with ground ice. The precipitated product canbe freed from the neutral fraction by dissolution in dilute sodiumhydroxide solution and extraction with ethyl ether. When acidified withdilute hydrochloric acid solution, the carboxylic acid precipitates outof the alkaline solution.

Example 32 G-NHCOCH₃ from G-Br

A suitable monobrominated heterodiamondoid G-Br (0.093 mole) isdissolved in 150 mL acetonitrile. While stirring, 30 mL concentratedsulfuric acid is slowly added to the above solution, whereby the mixtureheats up. After it has been left standing for about 12 hours, thesolution is poured into 500 mL ice water, whereby the monoacetaminoheterodiamondoid separates out in high purity.

Example 33 G-NHCHO from G-COOH

Within 7 minutes 8.16 g (0.17 mole) sodium cyanide and a suitablemonocarboxylated heterodiamondoid G-COOH (0.028 mole) are added to 100mL 100% sulfuric acid while stirring vigorously. After ½ hour,decomposition is carried out by pouring the reaction mixture onto 250 gcrushed ice which is then made basic by the addition of a sufficientamount of odium hydroxide solution and extracted five times withbenzene/ether. The solvent is removed in vacuo from the combinedextracts and the residue is recrystallized from benzene/hexane.

Example 34 G-CO₂CH₂CH₃ from G-COOH via G-COCl

0.017 mole of a suitable monocarboxylated heterodiamondoid G-COOH ismixed with 4.2 g PCl₅ in a 50-mL flask with a stirrer and a refluxcondenser. The reaction starts after 30-60 seconds with liquefaction ofthe reaction mixture. The mixture is heated for an additional about 1hour while stirring on the steam bath. The POCl₃ formed is distilled offunder vacuum. The acid chloride left behind as a residue is cooled withice water, and 6.0 mL absolute ethanol is added dropwise. The mixture isheated for an additional around 1 hour on the steam bath and then pouredinto 50 mL water after it has been cooled down. The ester is taken upwith ethyl ether and then washed with potassium carbonate aqueoussolution and water. After drying, fractionation is carried out overcalcium chloride under vacuum.

Example 35 G-CH═CH₂ from G-Br

Step 1: a solution of a suitable monobrominated heterodiamondoid G-Br(0.046 mole) in 15 mL n-hexane in a 150-mL three-necked flask equippedwith a stirrer, a gas inlet tube and a gas discharge tube with a bubblecounter is cooled to −20 to −25° C. in a cooling bath. While stirringone introduces 4.0 g powdered freshly pulverized aluminum bromide ofhigh quality, and ethylene is conducted in such a way that the gasintake can be controlled with the bubble counter. The reaction iscompleted after about 1 h. The reaction solution is decanted from thecatalyst into a mixture of ether and water. The ether layer is separatedoff, and the aqueous phase is extracted once more with ether. Thecombined ether extracts are washed with water and dilute sodiumcarbonate aqueous solution. After they have been dried over calciumchloride, the ether is distilled off. The residue is separated bydistillation under vacuum. Recrystallizing from methanol affordscrystals of the heterodiamondoidyl ethyl bromide G-CH₂CH₂Br.

Step 2: a solution of 0.7 g fine powdered potassium hydroxide and theabove heterodiamondoidyl ethyl bromide G-CH₂CH₂Br (0.012 mole) in 10 mLdiethylene glycol is heated to 220° C. in the oil bath for 6 hours.After cooling down the mixture is diluted with 30 mL water and exactedwith ethyl ether. The ether extract is washed twice with water and driedover calcium chloride. The residue left behind after the ether has beendistilled off is sublimated in vacuum, and if necessary, the compoundcan be recrystallized from methanol.

Example 36 G-C≡CH from G-Br

Step 1: in a 150-mL two-necked flask with a stirrer and a drying tube, amixture of 0.069 mole of a suitable monobromonated heterodiamondoid and20 mL vinyl bromide is cooled to −65° C. in a cooling bath. Whilestirring, 4.5 g powdered aluminum bromide is added in portions and themixture is stirred for an additional about 3 hours at the sametemperature. Then the reaction mixture is poured into a mixture of 30 mLwater and 30 mL ethyl ether. After vigorously stirring, the ether layeris separated and the aqueous layer is extracted once more with ether.The combined ether extracts are washed with water and dilute sodiumcarbonate solution. After it has been dried with calcium chloride andthe solvent has been distilled off, the residue is distilled undervacuum.

Step 2: 15 g powdered potassium hydroxide in 30 mL diethylene glycol isheated to reflux with 0.046 mole of the above product for about 9 hoursin the oil bath. Compound monoethynylated heterodiamondoid which isformed is then sublimated in the condenser and must be returned to thereaction mixture from time to time. At the end of the reaction time, thereaction mixture is distilled until no more solid particles go over. Thedistillate is extracted with ethyl ether and the ether phase is washedwith water and dried over calcium chloride. A short time after the etherhas been distilled off, the residue solidifies. It is sublimated undervacuum and, if necessary, recrystallized from methanol.

Example 37 G-O—CH₂—C₆H₅ from G-Br

To a solution of benzyl alcohol C₆H₅—CH₂—OH (0.28 mole) containing 0.03mole of sodium benzylate is added 0.01 mole of G-Br and the resultingmixture heated for about 4 hours, during which a copious precipitateNaBr formed. After cooling, the reaction mixture is poured into waterand the aqueous phase extracted with ethyl ether and the later driedover sodium sulfate, then evaporated. Most of the benzyl alcohol isremoved by distillation, leaving ca. 4 mL of oil which ischromatographed over alumina Elution with petroleum ether afford theproduct.

Example 38

Heterodiamondoidyl acetic acid, e.g. G-COOH is prepared as shown inExample 29. The corresponding acid chloride G-COCl is obtained bystirring a mixture of the acid and thioyl chloride diluted withpetroleum ether at room temperature for about 50 hours. Treatment of theacid chloride G-COCl with an excess amount of ethereal diazomethanegives the heterodiamondoidyl acetyl diazomethane G-COCHN₂. Reactions ofthe acid chloride G-COCl with such amines as ammonia and aniline givethe corresponding amides, in those cases G-CONH₂ and G-CONHC₆H₅respectively.

Example 39 G-CONH₂ from G-COCl

Concentrated aqueous ammonia (11.0 mL) is, over a period of 30 min.,stirred, drop by drop, into a stirred solution of G-COCl, prepared from5.5 mmole of G-COOH, in 4.0 mL of dry THF under cooling with ice-water.The stirring is continued for about 6 hours, and then, the precipitatesare filtered out. The addition of water to the filtrate gives the secondcrop. The combined precipitates are washed with water and dried to givethe title compound.

Example 40 Hofmann Reaction of G-CONH₂

Into an ice-cooled bromine-alkali reagent, freshly prepared from 1.0 gof bromine, 1.0 g of sodium hydroxide, and 10 mL of water, 0.5 g ofG-CONH₂ is added and stirred. The temperature is then slowly raised toabout 80° C. over a 3.5 hour period and kept there for about 10 min.After cooling, the separated solids are filtered and washed with water.Recrystallization from chloroform-petroleum ether gives the pure productG-NHCONHC(O)-G.

Example 41 G-N₃ from G-Br

A mixture of G-Br (2 mmole) and sodium azide (1.3 g) in dry dimethylsulfoxide (DMF, 20 mL) is heated with stirring at 100° C. for about twodays. The mixture is poured onto ice-water to give precipitates whichcan be purified by recrystallization from aqueous methanol to give thepure product.

Example 42 G-OCOCl from G-OH

To a solution of liquid phosgene (COCl₂, 30 g) in anhydrous benzene (100mL), a solution of G-OH (53 mmoles) and pyridine (7 g) in benzene (200mL) is added dropwise and with stirring over a 1 hour period, whilemaintaining the reaction temperature at about 4° C. when solidsprecipitate, additional benzene is added.

The reaction mixture is filtered and the filtrate is poured into icewater and shaken in a separatory funnel. The organic layer is dried withsodium sulfate and concentrated to about one-fifth of its originalvolume under reduced pressure at room temperature, and the concentratedsolution is stored in a freezer. The yield may be considered essentiallyquantitative for the purpose of synthetic use of the solution.

When a sample of the concentrate is evaporated to dryness at roomtemperature, the solid is obtained. Recrystallization from anhydrouspetroleum ether at low temperature, e.g. −20° C., may give crystals ofthe product.

Example 43 G-OCONHNH₂ from G-OCOCl and H₂NNH₂

A solution of G-OCOCl (9.3 mmoles) in anhydrous benzene (150 mL) isadded slowly to a stirred solution of anhydrous hydrazine (2.5 g) int-butyl alcohol (20 mL). After stirring for about 2 hours, the solventis removed in vacuo. The residue is dissolved in a mixture of ether (150mL) and water (10 mL). The ether layer is washed with 35 mL portions ofwater, 5 mL of 1% sodium carbonate solution, and 5 mL of water, anddried. Anhydrous hexane (10 mL) is added and the solution isconcentrated to about 10 mL. Cooling the solution at about −10° C. givesthe product G-OCONHNH₂.

Example 44 Heterodiamondoidyloxycarbonyl Amino Acids from G-OCOCl andAmino Acids

A suitable amino acid (5 mmoles) is suspended in water (about 20 mL).The mixture is stirred and cooled in an ice bath. Sodium hydroxide (1N,5 mL) is added whereupon the amino acid usually dissolved. To thismixture, 0.8 g sodium carbonate (7.5 mmoles) is added. From a solutionof G-OCOCl, the solvent is removed in vacuo on a flash evaporator at abath temperature of about 30° C. (the concentration of the chloroformatein the benzene solution is determined by removing the solvent from analiquot in vacuo at about 30° C. and weighting the residue). To theresidue which may be oily or semisolid, dry petroleum ether is added andremoved in vacuo. This is repeated once more to remove traces ofphosgene which may be left in the preparation of the chloroformate. Theresidue is dissolved in anhydrous dioxane (5 mL) and added in about fourportions to the solution of the amino acid over a period of about 1 hourwith continued stirring and cooling. If solid precipitates, ether isadded (5 mL) after the first and last addition of the chloroformate.After the addition of the chloroformate, the container of thechloroformate is washed twice with a small amount of dioxane. Afterstirring in ice for about 2 hours, the solution is extracted three timeswith ether or ethyl acetate, and under stirring and cooling acidifiedwith 85% phosphoric acid or 10% sulfuric acid to a pH of about 2. Theprecipitated product is extracted into the organic layer and the aqueousphase is extracted with two more portions of fresh organic solvent. Thecombined extracts are dried over sodium sulfate and the solvent isremoved in vacuo. The residue is recrystallized from a suitable solvent,e.g. ether-petroleum ether, ethyl acetate or ethyl acetate-petroleumether.

Example 45 G-POCl₂ from G-Br (FIG. 21)

0.1 mole of G-Br, 40 g (0.15 mol) of AlBr₃ and 200 mL of PCl₃ are heatedfor about 5 hours under reflux while being stirred. After cooling downand filtration, the residue is washed with 100 mL of benzene, suspendedin 300 mL of CCl₄ and decomposed carefully with water while cooling withice. The organic phase is separated out, washed with water, dried overCaCl₂ and concentrated in vacuum. Separation and purification of theproduct G-POCl₂ can be conducted by distilling the residue andrecrystallization from acetone. Please note that G-POCl₂ does notreaction with ethanol in pyridine or piperidine in benzene. Thus, 0.05mole of G-POCl₂ together with 9.2 g (0.2 mole) ethanol and 7.9 g (0.1mole) pyridine are heated under reflux for about 3 hours. Then thereaction mixture is poured onto ice while adding dilute hydrochloricacid. The product is filtered off and recrystallized from acetoneaffording the unreacted G-POCl₂. In addition, 0.05 mole of G-POCl₂ and17 g (0.2 mole) of piperidine are dissolved in 200 mL absolute benzene,and then heated for about 48 hours under reflux while stirring. Afterfiltration, the filtrate is concentrated to dryness affording theunreacted G-POCl₂.

20 mmoles of G-POCl₂ is heated for about 6 hours with 100 mL water underreflux. The aqueous solution is filtered after cooling, and the residueis recrystallized from glacial acetic acid affording the productG-PO(OH)₂.

Under nitrogen a solution of 0.1 mole of G-POCl₂ in 150 mL absoluteether is added dropwise over a period of about 2 hours to a suspensionof 7 g LiAlH₄ in 400 mL absolute ether. After the addition, the mixtureis stirred for an additional 1 hour under reflux. The excess LiAlH₄ isdestroyed by adding about 200 mL dilute hydrochloric acid. The organicphase is separated out, washed with water, dried over MgSO₄ andconcentrated under nitrogen. The residue is fractionated under nitrogenin vacuum to give the product G-PH₂.

About 50 mmoles of G-PH₂ is heated carefully at approximately 50° C.with 50 mL of 30% hydrogen peroxide (H₂O₂) until the reaction starts.Then the reaction mixture is diluted to one and half with water, boiledbriefly and filtered in hot. After cooling down it is possible toisolate some of the product G-P(OH)₂. The residue is extracted withCHCl₃ and then recrystallized from glacial acetic acid to give someadditional amount of the product.

0.05 mole of G-P(OH)₂ is added in small portions to 75 mL of PCl₃ within10 minutes. After the addition, the reaction mixture is stirred for anadditional 5 minutes. The phosphoric acid produced is separated out andthe residue is concentrated under vacuum and distilled to give theproduct G-PCl₂. Purification can be carried out by sublimating severaltimes to give a pure sample for analysis.

0.01 mole of G-PCl₂ is stirred in 50 mL water intensively for about 10hours at room temperature. Then the mixture is filtered and the residueis recrystallized several times from acetonitrile to yield the productG-P(OH)₂.

Example 46 G-SOCl from G and Subsequent Reactions (FIG. 22)

40 g (0.3 mole) of AlCl₃ and 200 mL of SOCl₂ are reacted at about −15°C. for about 2 hours with 0.3 mole of a heterodiamondoid. The mixture isstirred for an additional 1 hour at this temperature. Then the clearsolution is allowed to warm to room temperature, and the excess SOCl₂ isremoved under vacuum. The residue is taken up in 300 mL of CCl₄ andcarefully decomposed with water. The organic phase is separated out,washed with water, dried over CaCl₂ and concentrated in vacuum. Theresidue is distilled to give the product G-SOCl. Please note that G-Clis produced as the major by-product.

0.1 mole of G-SOCl is heated under reflux for about 6 hours with 200 mLof absolute methanol. The solvent is then removed in vacuum and theresidue is distilled to give the product. Further purification can becarried out by sublimation under vacuum.

0.1 mole of LiAlH₄ is suspended in 100 mL of absolute ether and heatedunder reflux for about 1 hour. Then a solution of 0.02 mole of G-SO₂CH₃in 100 mL of absolute ether is added dropwise over a period of about 2hours. After about additional 17 hours of stirring under reflux, theexcess LiAlH₄ is decomposed with a saturated Na₂SO₄ solution, and theether phase is separated out after 100 mL of concentrated hydrochloricacid has been added. The aqueous phase is washed for an additional twotimes with ether. The extracts are combined and dried over CaCl₂ andconcentrated under vacuum. The residue is sublimated to give G-SH.

To 650 mL 5% sodium hydroxide solution is added about 0.25 mole ofG-SOCl (crude product) at room temperature. After about 5 hours ofintense stirring, the temperature is increased slowly to about 50° C.,then filtration. Approximately 12% chlorination products remain asresidue. The filtrate is acidified with concentrated hydrochloric acidwhile cooling with ice, and extracted several times with ether. Thecombined extracts are washed with water, dried over MgSO₄ andconcentrated to a dry product. Recrystallization from acetonitrile givesa pure product G-SO₂H.

5 mmoles of G-SO₂H is suspended in 25 mL water while adding 1 mL 30%hydrogen peroxide. Then the mixture is heated while stirring on a waterbath and an additional 3 mL 30% hydrogen peroxide are added dropwisewithin 30 minutes. The solution is briefly boiled, filtered andconcentrated under vacuum to dryness at about 30° C. to give theheterodiamondoidyl sulfonic acid monohydrate G-SO₃H.H₂O.

0.1 mole of G-SH dissolved in 100 mL ethanol is added while stirringinto a solution of 8 g (0.2 mole) of NaOH in 200 mL water and treatedfor about 1 hour at 50° C. with 15.4 g (0.1 mole) of diethylsulfate.After an additional 1 hour stirring under reflux, the reaction mixtureis cooled down and extracted several times with ether. The combinedextracts are concentrated in vacuum and the residue is distilled overCaCl₂ to give the product G-SC₂H₅.

0.05 mole of G-SC₂H₅ in 100 mL glacial acetic acid is heated to refluxwith 17.5 g (0.15 mole) 30% hydrogen peroxide. After about 1 hour ofstirring under reflux, the reaction mixture is poured onto ice andfiltered. Recrystallization from ethanol/water gives the productG-SO₂C₂H₅.

0.02 mole of G-SO₂C₂H₅ and 12 g KOH are heated to 250° C. with 3-5 dropsof water. Then the temperature is raised to 275° C. in the course ofabout 45 minutes, whereby a strong development of a gas takes place.After cooling down, the mixture is dissolved in a little water,acidified with concentrated hydrochloric acid while cooling with ice andextracted several times with ether. The distillation residue from theether extract gives, after recrystallization from acetonitrile, a pureproduct of G-SO₂H.

0.05 mole of G-SO₂H is left standing over night with 100 mL freshlydistilled SOCl₂ at room temperature. The excess SOCl₂ is carefullyremoved under vacuum, and the residue is distilled, whereby the productG-SOCl solidifies in the receiver.

0.1 mole of G-SOCl together with 200-300 mL absolute alcohol and 7.9 g(0.1 mole) pyridine is heated for 8-12 h under reflux. The excessalcohol is then removed under vacuum and the residue is mixed withether. The ether solution is washed twice with dilute hydrochloric acidand water, dried over MgSO₄ and concentrated. The residue is distilledto give the corresponding ester.

45 mmoles of G-SOCl is heated with 300 mL 25% aqueous ammonia or 150 mL40% aqueous dimethylamine for about 2 hours while stirring under reflux.Then the reaction mixture is concentrated to dryness in vacuum and theresidue is extracted with ether. The distillation residue from the etherextract is recrystallized from cyclohexane to afford the correspondingamide.

Into a clear solution of 0.05 mole G-SO₂H and 2 g (0.05 mole) NaOH in200 mL water is introduced a strong chlorine gas flow at approximately5° C. temperature increase within 45 minutes. After filtration, theresidue is extracted in ether. The ether solution is washedchlorine-free with NaHSO₃ solution, dried over MgSO₄ and concentrated todryness in vacuum at room temperature. Recrystallization from ethanolgives the product G-SO₂Cl. Further recrystallization several times frompetroleum ether can afford a pure sample for analysis.

0.01 mole G-SO₂Cl in 100 mL absolute ether is added dropwise within 1hour to a suspension of 3 g LiAlH₄ in 100 mL absolute ether. After theaddition, the reaction mixture is stirred for about 3 hours underreflux, then the excess LiAlH₄ is destroyed with dilute hydrochloricacid. The organic phase is separated out, dried over MgSO₄ andconcentrated. The residue is sublimated several times to give G-SH.

10 mmoles G-SO₂Cl and 100 mL 10% sodium hydroxide solution are heated ona water bath for about 4 hours while adding 1 g pyridine. After coolingand filtration, the filtrate is acidified with concentrated hydrochloricacid and perforated over night with ether. The ether extract is driedover MgSO₄ and concentrated to yield G-SO₂H.

20 mmoles G-SO₂Cl together with 30 mL absolute methanol and 3 g pyridineis heated for about 4 hours at 50° C. while stirring vigorously. Thenthe reaction mixture is poured on ice and extracted with ether. Theether solution is washed with dilute hydrochloric acid, dried over MgSO₄and concentrated. The residue is sublimated to give G-Cl.

10 mmoles G-SO₂Cl and 100 mL 25% aqueous ammonia are heated on a waterbath for about 3 hours while stirring. The solution is concentrated invacuum to dryness, and the residue is sublimated to give G-OH.

0.02 mole of the corresponding hetero diamondoidyl sulfinic acid esteror amide is treated in 150-400 mL acetone at reflux with a saturatedsolution of KMnO₄ in acetone until a violet color remains. After anadditional 30 minutes of stirring under reflux, the reaction mixture isfiltered from MnO₂ and the residue is extracted several times withacetone. The combined filtrates are then concentrated in vacuum to givethe corresponding hetero diamondoidyl sulfonic acid esters or amides.

Example 47 G-G from G-Br

A monobrominated heterodiamondoid G-Br (50 mmole) is dissolved in 30 mLof xylene and heated to reflux in a three-necked flask fitted withthermometer, nitrogen inlet, stirrer, and reflux condenser, under a slowstream of nitrogen. Then a total of 1.15 g of small pieces of sodiummetal is added to the stirred reaction mixture over a period of about 4hours. After all sodium has been added, the mixture is refluxed forabout an additional hour and then filtered in the hot state. On coolingto room temperature, the product G-G is crystallized from the filtrate.This G-G product can itself be dibrominated and thereafter converted todicyano, decarboxyl diamino and diacetamido derivatives as desired.

Example 48 CH₃OC₆H₄-G-G-C₆H₄OCH₃ from Br-G-G-Br

To Br-G-G-Br (11.5 mmole) is added 25 mL of anisole and the mixture isheated to reflux (about 155° C. pot temperature) for about 5 hours.After about 15 minutes refluxing, hydrogen bromide is evolved. Theevolution of hydrogen bromide is ceased after about 1 hour. The reactionproduct is filtered hot and on cooling to room temperature, a crudeproduct is collected which is then recrystallized from xylene to givethe pure product CH₃OC₆H₄-G-G-C₆H₄OCH₃.

Example 49 HClH₂NCH₂-G-G-CH₂NH₂HCl and H₂NCH₂-G-G-CH₂NH₂ from NC-G-G-CN

Powdered lithium aluminum hydride (0.6 g) is charged into a three-neckflask fitted with a thermometer, nitrogen inlet, addition funnel, andreflux condenser together with 15 mL of anhydrous THF. A solution ofNC-G-G-CN (7.8 mmole) in 20 mL of anhydrous THF is added over a periodof about 20 min. the reaction product, after cooling to roomtemperature, is poured onto ice containing dilute hydrochloric acid.Recrystallization from dilute hydrochloric acid gives thedihydrochloride product HClH₂NCH₂-G-G-CH₂NH₂HCl. The free diamineH₂NCH₂-G-G-CH₂NH₂ is obtained from the dihydrochloride by reaction withammonia.

Design of Heterodiamondoid-Containing Polymers or Co-Polymers

Polymers such as polyamides, polyimides, polyesters, polycarbonateswhich are easily processed soluble, mechanically strong and thermallystable are very important materials in a wide range of industries, suchas the microelectronics industry. Introduction of different pendantgroups such as heterodiamondoid groups along the polymer backbone canimpart greater solubility and enhanced rigidity as well as bettermechanical and thermal properties of the resulting polymers. Ofparticular interest is introducing such heteroatom-containing cagehydrocarbons into the polymer chain because such cardo groups showsignificant characteristics such as high cardo/hydrogen ratio, highthermal and oxidative stability, rigidity, hydrophobicity, andtransparency. They also can impart desired electrical and opticalproperties to the polymers.

Example 50 Polymerization of Diacrylated Heterodiamondoids

The following compositions are subjected to polymerization: diacrylatedheterodiamondoid; monoacrylated heterodiamondoid; a 50:50 mixture byweight of monoacrylated heterodiamondoids and methyl methacrylate; and,a 50:50 mixture by weight of monoacrylated heterodiamondoid anddiethylene glycol bis allylcarbonate. To the various compositions isadded 0.1 part by weight of a photo-polymerization initiator(benzophenone). The mixture is applied to a glass plate andphoto-polymerized by irradiation with ultraviolet light.

Example 51 Polymerization of Diethynylated Heterodiamondoids

A sample of a diethynylated heterodiamondoid (275 mg) is sealed in aglass tube and heated to 200° C. for 14 hours and at 250° C. for 48hours. The tube is cooled to room temperature and opened to afford apolymeric resin.

Example 52 Polyesters Derived from2,2-Bis(4-hydroxyphenyl)Heterodiamondoids by Solution Polycondensation

A 2,2-bis(4-hydroxyphenyl)heterodiamondoid (0.005 mole) is mixed withpyridine (2 mL) at room temperature for about 20 minutes. Terephthaloylchloride (1.015 g, 0.005 mole) in nitrobenzene (20 mL) is added to theabove solution at room temperature for about 5 minutes and then themixture is heated to about 150° C. for about 10 hours. The resultingpolymer solution is poured into methanol to precipitate the polymer. Thepolymer is washed with hot methanol, collected on a filter, and dried invacuo at about 60° C. for about 24 hours.

Example 53 Polyamides Derived from2,2-Bis[4-(4-aminophenoxy)phenyl]Heterodiamondoids by SolutionPolycondensation

A flask is charged with a mixture of a2,2-bis[4-(4-aminophenoxy)phenyl]heterodiamondoid (0.9 mmol),terephthalic acid (0.149 g, 0.9 mmol), triphenyl phosphite (0.7 mL),pyridine (0.6 mL), N-methyl-2-pyrrolidone (NMP, 2 mL) and calciumchloride (0.25 g). It is refluxed under argon for about 3 hours. Aftercooling, the reaction mixture is poured into a large amount of methanolwith constant stirring, producing a precipitate that is washedthoroughly with methanol and hot water, collected on a filter, and driedto afford a polyamide containing heterodiamondoid components along thepolymer chain.

Example 54 Polyimides Derived from2,2-Bis[4-(4-aminophenoxy)phenyl]Heterodiamondoids by ChemicalImidization

To a stirred solution of a2,2-bis[4-(4-aminophenoxy)phenyl]heterodiamondoid (1.2 mmol) in DMAc (7mL) is gradually added pyromellitic dianhydride (0.262 g, 1.2 mmol). Themixture is stirred at room temperature for 2-4 hours under argonatmosphere to form the poly(amic acid). Imidization is carried out byadding DMAc and an equimolar mixture of acetic anhydride and pyridineinto the above-mentioned poly(amic acid) solution with stirring at roomtemperature for about 1 hour and then heating at about 100° C. for anadditional about 3 hours. The reaction product is subsequently pouredinto methanol and the precipitate is filtered off, washed with methanoland hot water, and dried to afford the polyimide containingheterodiamondoid components along the polymer chain.

Example 55 Polyimides Derived from2,2-Bis(4-aminophenyl)Heterodiamondoids by Chemical Imidization

To a solution of a 2,2-bis(4-aminophenyl)heterodiamondoid (5 mmol) in17.9 mL of NMP, 3,3′,4,4′-benzophenonetetracarboxylic dianhydride (BTDA,98.6%, 1.61 g, 5 mmol) is added with a solid content of 15 wt %. Thesolution is continuously stirred at room temperature for about 24 hours.To the reaction mixture are added 1.5 mL of acetic anhydride and 2.0 mLof pyridine and then the temperature is raised to about 120° C. and keptat this temperature for about 3 hours. The resulting solution is pouredinto excess methanol and filtered. The precipitated polymer is washedseveral times with water and methanol, and then the polymer is dried atabout 100° C. for around 12 hours in vacuo.

Example 56 Polyimides Derived from2,2-Bis(4-aminophenyl)Heterodiamondoids by Solution Polymerization

To a solution of a 2,2-bis(4-aminophenyl)heterodiamondoid (5 mmol) in 19mL of freshly distilled m-cresol, 3,3′,4,4′-benzophenonetetracarboxylicdianhydride (98.6%, 1.61 g, 5 mmol) and isoquinoline (0.95 mL) as acatalyst are added at room temperature under nitrogen atmosphere. Thereaction mixture is heated to about 70˜80° C. over 2 hours and kept atthis temperature for about 2 hours. Afterwards, the solution temperatureis slowly raised to about 200° C. over 2 hours and refluxed for 6 hours.The polymerization is performed under a gentle nitrogen stream to removethe water produced during imidization. Work-up is done by pouring theresulting solution into excess methanol and filtering. The precipitatedpolymer is washed several times with water and methanol, and then thepolymer is dried at about 100° C. for around 12 hours in vacuo.

Example 57 Linear Polyaspartimides Derived from2,2-Bis[4-(4-aminophenoxy)phenyl]Heterodiamondoids by the MichaelAddition Reaction

In a 100 mL three necked flask equipped with a magnetic stirrer, areflux condenser, thermometer and nitrogen inlet, 0.553 g (1.25 mmol) ofbis(3-ethyl-5-methyl-4-maleimidophenyl)methane (BEMM) is added to 3.5 mLof m-cresol. When all the BEMM is dissolved, 1.25 mmol of a diamine2,2-bis[4-(4-aminophenoxy)phenyl]heterodiamondoid is added. Then 0.1 mLof glacial acetic acid, used as a catalyst, is added into the mixture sothat the above diamine is completely dissolved. The reaction mixture isthen immersed in an oil bath maintained at 100-110° C. for about 100hours to polymerize. The resulting polymer is isolated by pouring theviscous reaction mixture into excess ethanol under vigorous stirring.The polymer precipitate is collected by filtration and washed thoroughlywith ethanol and extracted with hot ethanol using a Soxhlet extractorand subsequently dried in a vacuum oven at 70° C. for about 24 hours.

Example 58 4-(1-Heterodiamondoidyl)-1,3-Benzenediols from BrominatedCompounds and subsequent reactions

A suitable brominated heterodiamondoid (0.046 mole), resorcinol (5.51 g,0.05 mole), and benzene (50 mL) are combined in a reaction flaskequipped with a nitrogen inlet, a condenser fitted with a causticscrubber, and a stirrer. This mixture is heated to reflux and for about72 hours to allow for reaction under a constant nitrogen purge to assistin the removal of HBr formed. The reaction mixture is cooled to ambienttemperature and the hetero diamondoidyl substituted resorcinol iscrystallized from solution. Residual resorcinol is removed byprecipitating a solution of the product in methanol into warm waterfollowed by filtrating and washing with water. Subsequent purificationto a polymerization quality monomer is accomplished by vacuum drying toremove residual water, recrystallizing from toluene, and finallysubliming to afford the product which is used in the followingreactions.

A mixture of a 4-(1-heterodiamondoidyl)-1,3-benzenediol (13 mmol),p-chloronitrobenzene (4.53 g, 28.8 mmol), potassium carbonate (4.3 g,31.2 mmol) and dry N,N-dimethylformamide (DMF, 30 mL) is refluxed forabout 8 hours. The mixture is then cooled and poured into amethanol-water solution (1:1 by volume). The crude product isrecrystallized from glacial acetic acid.

Hydrazine monohydrade (10 mL) is added dropwise to a mixture of theabove product (4-(1-heterodiamondoidyl)-1,3-bis(4-nitrophenoxy)benzene,12.3 mmol), ethanol (25 mL), and a catalytic amount of 10% palladium onactivated carbon (Pd/C, 0.05 g) at the boiling temperature. The reactionmixture is refluxed for about 24 hours, and the diamine product isprecipitated during this period. The mixture is then added to asufficient amount of ethanol to dissolve the diamine product andfiltered to remove Pd/C. After cooling, the recipitated crystals areisolated by filtration and recrystallized from 1,2-dichlorobenzene toafford a pure diamine product.

A flask is charged with 1.73 mmol of a4-(1-heterodiamondoidyl)-1,3-bis(4-aminophenoxy)benzene, 0.68 g (3.54mmol) of trimellitic anhydride, and 5 mL of DMAc. The mixture is stirredat room temperature for about 5 hours under argon atmosphere. Whilecontinuing to maintain agitation and room temperature, 2.4 mL of aceticanhydride and 1.5 mL of pyridine are added incorporating for about 1hour. Afterwards the mixture is heated at 100° C. for about 4 hours andthen cooled and poured into methanol. The precipitate is filtered offand is purified by extraction with hot ethanol using a Soxhlet extractorand subsequently dried in a vacuum oven at 70° C. for 24 hours to afforddiimide-dicarboxylic acid: 4-(1-heterodiamondoidyl)-1,3-bis(4-trimellitimidophenoxy)benzene.

A mixture of the diimide-dicarboxylic acid(4-(1-heterodiamondoidyl)-1,3-bis(4-trimellitimidophenoxy)benzene, 0.7mmol), 0.362 g of a diamine(2,2-bis[4-(4-aminophenoxy)phenyl]hexafluoropropane, 0.7 mmol), 0.25 gof calcium chloride, 0.6 mL of triphenyl phosphite, 0.6 mL of pyridine,and 3.0 mL of NMP is heated with stirring at 100° C. for about 2 hoursunder argon stream. After cooling, the reaction mixture is poured into alarge amount of methanol with constant stirring, producing a precipitatethat is washed thoroughly with hot water and methanol, collected on afilter, and dried at 100° C. under vacuum for 24 hours to afford a purepolyamide-imide containing heterodiamondoid components in the polymerbackbone.

A 4-(1-heterodiamondoidyl)-1,3-benzenediol (20.5 mmol) and4,4′-difluorobenzophenone (4.468 g, 20.5 mmol) mixture is dissolved in35 mL DMAc and 10 mL toluene in a reaction flask fitted with a nitrogenblanket, mechanical stirrer, and a Dean-Stark trap. To this mixtureK₂CO₃ (2.969 g, 21.48 mmol) is added while stirring and heating toreflux. Reflux is held at around 130° C. for about 1 hour followed bythe gradual removal of toluene from the reaction flask until the flasktemperature reaches around 160° C. (ca. 2 hours). The reaction mixtureis maintained at 160° C. for 10 hours and then cooled to ambienttemperature. The polymer solution is diluted with chloroform, filteredto remove the inorganic salts, acidified, and then precipitated intomethanol. Filtration and drying of the product at about 120° C. undervacuum gives the homopolymer.

Example 59 Co-Polymerization from4-(1-Heterodiamondoidyl)-1,3-Benzenediols and2,2-Bis(4-Hydroxyphenyl)propane by Nucleophilic Aromatic Substitution

Co-polymerizations are carried out with different molar ratios ofco-monomers (2,2-bis(4-hydroxyphenyl)propane and a4-(1-heterodiamondoidyl)-1,3-benzenediol) using either DMAc ortetramethylene sulfone (sulfolane) as solvent. For instance, a4-(1-hetero diamondoidyl)-1,3-benzenediol (10.25 mmol) and2,2-bis(4-hydroxyphenyl)propane (10.25 mmol) and4,4′-difluorobenzophenone (4.468 g, 20.5 mmol) can be dissolved in 35 mLDMAc and 10 mL toluene in a reaction flask fitted with a nitrogenblanket, mechanical stirrer, and a Dean-Stark trap. To this mixtureK₂CO₃ (2.969 g, 21.48 mmol) is added while stirring and heating toreflux. Reflux is held at around 130° C. for about 1 hour followed bythe gradual removal of toluene from the reaction flask until the flasktemperature reaches around 160° C. (ca. 2 hours). The reaction mixtureis maintained at 160° C. for 10 hours and then cooled to ambienttemperature. The polymer solution is diluted with chloroform, filteredto remove the inorganic salts, acidified, and then precipitated intomethanol. Filtration and drying of the product at about 120° C. undervacuum gives the copolymer. If sulfolane is used as the solvent, theco-polymers are Soxhlet extracted with methanol to remove solvent andsalts from the insoluble polymer.

Example 60 Poly(3-benzyloxypropyl malate-co-ethyl heterodiamondoidylmalate (85/15) from 3-Benzyloxypropylmalolactonate and EthylHeterodiamondoidyl Malolactonate by Anionic Ring-OpeningCo-Polymerization

A flask is charged with a mixture of 3-benzyloxypropylmalolactonate (85mol %), ethyl heterodiamondoidyl malolactonate (15 mol %) andtetraethylammonium benzoate (10⁻³ eq. per mole of total moles of theco-monomers, acting as an initiator of the anionic ring-openingco-polymerization) under nitrogen. The mixture is then well stirred andwarmed to 37° C. under nitrogen atmosphere and is maintained at thistemperature for 15 days. After completion of the co-polymerizationreaction, the co-polymers are collected and washed with small amount ofwater, ethanol, and dried in vacuum for about 24 hours.

Example 61 Phenyl Heterodiamondoid-Modified PEGs [Poly(ethyleneglycol)s] from Alcoholate of Heterodiamondoidylphenol

To a stirred solution of a poly(ethylene glycol) (PEG, 1 mmol) in 15 mLdichloromethane, 1 mL of triethylamine is added. This solution is cooledin an ice bath under nitrogen atmosphere. Then 1 g of4-toluenesulfonylchloride (5.2 mmol) is added. The reaction is continuedat 0° C. for 2 hours and then the mixture stirred at room temperatureovernight. The product is precipitated in diethyl ether. An additionalrecrystallization from ethanol is performed in order to remove thetriethylammonium chloride formed during the reaction affording a purePEG tosylate.

Under a nitrogen atmosphere, a heterodiamondylphenol (4 mmol) dissolvedin 70 mL of freshly distilled dichloromethane is added dropwise to 0.24g of sodium hydride suspended in 30 mL of distilled dichloromethane. Thesolution is stirred for 2 hours at room temperature before addingdropwise the PEG tosylate (a little excess) dissolved in 50 mL ofdichloromethane. The reaction mixture is kept at 40° C. for 24 hours.The obtained polymer is precipitated in ethyl ether, recrystallized fromethanol and stored at 4° C.

Example 62 Water Soluble Poly(ethylene glycol)s (PEGs) ContainingHeterodiamondoids for Potential Drug Delivery Purposes

Host-guest interactions are very important processes in human biology.The water solubility of drugs is a key factor in determining theirmedical efficacy in living tissue. In order to enhance drug efficiency,poly(ethylene glycol)s (PEGs) can be modified by heterodiamondoidhydrocarbon compounds at their OH terminal ending(s). These hydrophobicgroups may be selected based upon their potentially strong interactionswith other groups in “cavities” formed in PEG polymer chains and thuscan help deliver the drugs which have low solubility in water. Examplesare shown in FIG. 28.

Example 63 Carbon-Rich Polymers for Nanolithography

Rapid advances in the miniaturization of microelectronic devices requirethe development of new imageable polymeric materials for 193 nmmicrolithography (The National Technology Roadmap for Semiconductors,Semiconductor Industry Association (SIA), San Jose, Calif., 1997). Thedesign challenge for 193 nm resist materials is the trade-off betweenplasma-etch resistance (which requires a high carbon/hydrogen ratio inthe polymer structure) and optical properties for lithographicperformance

FIG. 29 shows the design of a carbon-rich cyclopolymer incorporatingboth imageable functionalities (tert-butyl esters) for chemicalamplification, and high etch-resistance moieties (heterodiamondoidsbased on tetramantanes, pentamantanes, hexamantanes and the like). Toadjust the physical properties of polymers, such as wettability andadhesion properties, a wide range of co-polymers can be prepared. Thiswas shown to be feasible for adamantane-containing cyclopolymers andco-polymers by D. Pasini, E Low and J. M. J. Fréchet (AdvancedMaterials, 12, 347-351 (2000)), and those materials showed excellentimaging properties. In addition, since the synthetic routes involve freeradical polymerization techniques, metal contamination of the underlyingsemiconductor substrates is not an issue, as is the case for polymersbased on norbornene (Chemical of Materials, 10, 3319 (1998); 10, 3328(1998)). Furthermore, adamantane-containing polymers show high glasstransition temperatures (T_(g)) and high deposition temperature (T_(d))and good film-forming properties. Polymers based on heterodiamondoidswould be expected to have even better properties.

Example 64 Soluble Heterodiamondoid-Containing Polyesters Based onHeterodiamondoid Bisphenol

Polyarylates derived from bisphenol and iso/terephthalic acid are wellaccepted as highly thermally stable materials. However, polyarylates aregenerally difficult to process because of their limited solubility inorganic solvents and their high melting temperatures or high T_(g)'s byvirtue of their rigid structures. It has been reported thatincorporation of bulky pendant cardo groups, such as adamantyl groups,into polymer backbones, results in enhanced thermal properties of thepolymers compared with polymers containing aromatic bisphenols. As anexample of this type of polymer, FIG. 26 shows the design of suchpolyesters.

Example 65 Soluble Heterodiamondoid Containing Polyamides Based onHeterodiamondoid Diamines

Aromatic polyamides attract much interest because of theirhigh-temperature resistance and mechanical strength. However, theapplications of polyamides are limited by processing difficultiesarising from their low solubility in organic solvents and their highglass transition or melting temperature. A number of successfulapproaches to increasing the solubility and processability ofpolyamides, without sacrificing their thermal stability, employ theintroduction of flexible or non-symmetrical linkages into the polymerbackbone or the incorporation of bulky substituents, such as pendantgroups, into the polymer backbone. The inter-chain interaction of thepolymers can be decreased by the introduction of bulky pendant groups,resulting in improved solubility of the polymers. Generally, theincorporation of pendant groups results in amorphous materials withincreased solubility in common organic solvents.

FIG. 27 presents an example of this design which incorporatesheterodiamondoid groups in the polyamide backbone.

Example 66 Soluble Heterodiamondoid-Containing Polyimides Based onHeterodiamondoid Diamines

The outstanding properties of aromatic polyimides, such as excellentthermo-oxidative stability and superior chemical resistance, led to theuse of polyimides in many applications such as insulating materials forelectronics, semipermeable membranes for gas separations, andhigh-temperature adhesives and coatings (J. M. Sonnett, T. P. Gannett,Polyimides: Fundamental and Applications, M. K. Ghosh and K. L. Mittal,Ed., Marcel Dekker, New York, 1996). However, in general, aromaticpolyimides are insoluble and intractable and are, only processable underextreme conditions. To overcome these processing problems,heterodiamondoid groups can be placed in polyimide polymer backbone(FIG. 28), and in polyaspartimides (FIG. 29).

Example 67 Soluble Heterodiamondoid Containing Polyamide-Imides Based onHeterodiamondoid Diamide-Dicarboxylic Acids and Diamines

Aromatic polyimides are recognized as a class of high performancematerials because of their remarkable thermal and oxidative stabilitiesand their excellent electrical and mechanical properties, even duringlong periods of operation. Unfortunately, strong interactions betweenpolyimide chains and their rigid structure make them intractable. Poorthermoplastic fluidity and solubility are the major problems for wideapplications of polyimides. On the other hand, polyamides have theadvantage of good solubility and processability, as do polyetherimides.Therefore, polyamide-imide or polyetherimide might be the most usefulmaterials, combining the advantages of both polyimides (such ashigh-temperature stability) and polyamides (such as goodprocessability). In combination with the advantages of diamondoidhydrocarbons, we present a sample design of a polyamide-imide containingheterodiamondoid groups in the polymer chain (FIG. 30). The diaminesinvolved in the polymerization reaction could be either heterodiamondoiddiamines such as shown in FIG. 29 or other aromatic diamines

1. A heterodiamondoid compound of the following Formula I:

wherein: G is a diamondoid nucleus selected from a triamantane or higherdiamondoid nucleus having 1 to 20 heteroatoms selected from the groupconsisting of boron, silicon, oxygen, sulfur, nitrogen, phosphorus,selenium, aluminum, and arsenic; and R¹, R², R³, R⁴, R⁵, and R⁶ are eachindependently hydrogen or a covalently bonded functional group, providedthat the covalently bonded functional group comprises a heteroaryl orheterocycle moiety.
 2. The heterodiamondoid compound of claim 1 whereinat least one secondary carbon in the diamondoid nucleus is replaced by aheteroatom.
 3. The heterodiamondoid compound of claim 1 wherein at leastone tertiary carbon in the diamondoid nucleus is replaced by aheteroatom.
 4. The heterodiamondoid compound of claim 1 having oneheteroatom.
 5. The heterodiamondoid compound of claim 1 having more thanone heteroatoms.
 6. The heterodiamondoid compound of claim 1 having fromtwo to twenty heteroatoms.
 7. The heterodiamondoid compound of claim 1wherein the diamondoid nucleus is a triamantane nucleus.
 8. Theheterodiamondoid compound of claim 1 wherein the diamondoid nucleus is ahigher diamondoid nucleus.
 9. The heterodiamondoid compound of claim 1wherein at least one of the heteroatoms replacing a carbon atom is anelectron-donating heteroatom.
 10. The heterodiamondoid compound of claim9, wherein the electron-donating heteroatom is sp³-hybridized in thediamond lattice.
 11. The heterodiamondoid compound of claim 1 wherein atleast one of the heteroatoms replacing a carbon atom is anelectron-withdrawing heteroatom.
 12. The heterodiamondoid compound ofclaim 11 wherein the electron-withdrawing element is boron.
 13. Theheterodiamondoid compound of claim 11 wherein the electron-withdrawingheteroatom occupies a substitutional site on the diamond lattice. 14.The heterodiamondoid compound of claim 11 wherein theelectron-withdrawing heteroatom is sp³-hybridized in the diamondlattice.
 15. The heterodiamondoid compound of claim 1 wherein at leastone of R¹, R², R³, R⁴, R⁵, and R⁶ is a convalently bonded functionalgroup.
 16. The heterodiamondoid compound of claim 7 wherein at least oneof R¹, R², R³, R⁴, R⁵, and R⁶ is a convalently bonded functional group.17. The heterodiamondoid compound of claim 8 wherein at least one of R¹,R², R³, R⁴, R⁵, and R⁶ is a convalently bonded functional group.
 18. Theheterodiamondoid compound of claim 15 wherein the covalently bondedfunctional group comprises a group selected from the group consisting ofhalo, thio, oxide, hydroxyl, nitro, sulfonylhalide, sulfonate,phosphine, added alkyl, alkenyl, alkynyl and aryl, with or withoutsubstitution.
 19. The functionalized heterodiamondoid compound of claim15 wherein the one or more functional groups comprise a halo.
 20. Thefunctionalized heterodiamondoid compound of claim 15 wherein the one ormore functional groups comprise a hydroxide.
 21. The functionalizedheterodiamondoid compound of claim 15 wherein the one or more functionalgroups comprise an oxide.
 22. The functionalized heterodiamondoidcompound of claim 15 wherein the one or more functional groups comprisea nitrate.
 23. The functionalized heterodiamondoid compound of claim 15wherein the one or more functional groups comprise a group selected fromthe group consisting of haloalkyl; haloalkenyl; haloalkynyl;hydroxyalkyl; alkylthio; alkoxy; aminoalkyl; aminoalkoxy; cycloalkyloxy;aryloxy; —C(O)Z; —CO₂Z; —R⁷COZ wherein R⁷ is alkenyl, aminoalkenyl, orhaloalkenyl; —R⁷COOZ; —OSO₃H; NH₂; NHR′; NR′R″; and N⁺R′R″R′″ whereinR′, R″, and R′″ are independently alkyl, thio, thioalkyl, heteroalkyl,or aryl, R⁸NHCOR⁹ wherein R⁸ is selected from the group consisting ofCH₂, OCH₂, NHCH₂, CH₂CH₂, and OCH₂CH₂ and R⁹ is selected from the groupconsisting of alkyl, aryl, and aralkyl, and R¹⁰CONHR¹¹ wherein R¹⁰ isselected from the group consisting of CH₂, OCH₂, NHCH₂, CH₂CH₂, andOCH₂CH₂, and R¹¹ is selected from the group consisting of alkyl, aryl,and aralkyl, wherein Z is hydrogen, alkyl, halo, haloalkyl, halothio,amino, monosubstituted amino, disubstituted amino, cycloalkyl, or aryl.24. The heterodiamondoid compound of claim 15, wherein the one or morefunctional groups comprise a polymerizable functional group.
 25. Theheterodiamondoid compound of claim 1 as a discrete molecule.
 26. Theheterodiamondoid compound of claim 1 as a crystal.
 27. Theheterodiamondoid compound of claim 1 having from 1 to 6 heteroatoms. 28.The heterodiamondoid compound of claim 1, wherein 1 to 6 carbon atomsare replaced by heteroatoms.
 29. The heterodiamondoid compound of claim9, wherein the electron-donating heteroatom is selected from the groupconsisting of nitrogen, phosphorus, and arsenic.
 30. Theheterodiamondoid compound of claim 9, which is an aza-diamondoid.